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TerminatedNCT02994953COMBOUpdated Sep 20, 2024Results posted

A Phase Ib Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) of Avelumab in Combination With M9241(NHS-IL12) (JAVELIN IL-12)

A Phase 1 interventional study of Avelumab and M9241 in Advanced Solid Tumors, sponsored by EMD Serono Research & Development Institute, Inc.. Terminated at 33 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-20.

Sponsored by EMD Serono Research & Development Institute, Inc. · Phase 1, Interventional, and Treatment

Why this study was terminated
The study was terminated due to pre-specified futility criteria met.
Phase
Phase 1
Study type
Interventional
Enrollment
52
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The study consisted of 2 parts: Dose Escalation phase (Part A) and Expansion phase (Part B). The dose escalation phase evaluated the safety, tolerability, and PK of avelumab in combination with M9241 in subjects with locally advanced, unresectable, or metastatic solid tumors. Expansion phase assessed the safety and clinical activity of the combination regimen in selected tumor types. In Expansion phase subjects who had completed the combination treatment of avelumab at a given dose level of M9241, a safety review was performed by the Safety monitoring committee in order to make a decision on the next dose level. Successive cohorts of 3 to 6 subjects were treated with escalating doses of M9241 with avelumab intravenous (IV).

02

Conditions studied

  • Advanced Solid Tumors

Keywords

  • Avelumab
  • M9241
  • NHS-IL12
  • Advanced Solid Tumors
03

In context

Lead sponsor

EMD Serono Research & Development Institute, Inc. is the lead sponsor of 85 studies on the registry; 8 are open to participants now.

Of its 46 completed or terminated interventional studies of FDA-regulated products, 38 (83%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Part A:

  • subjects must had signed written informed consent.
  • male or female subjects age greater than equals to (>=)18 years.
  • subjects must had histologically or cytologically proven metastatic or locally advanced solid tumors for which no standard therapy exists, standard therapy had failed, subject was intolerant of established therapy known to provided clinical benefit for their condition, or standard therapy was not acceptable to subject.
  • subjects who had been treated previously with a checkpoint inhibitor may enroll (except as outlined below for expansion cohorts).
  • at least 1 unidimensional radiographically measurable lesion based on response evaluation criteria in solid tumors (recist) version 1. 1 (v1. 1), except for subjects with metastatic castration-resistant prostate cancer (crpc) or metastatic breast cancer who may been enrolled with objective evidence of disease without a measureable lesion. - eastern cooperative oncology group (ecog) performance status of 0 to 1 at screening
  • estimated life expectancy of more than 12 weeks

  • adequate hematological function as defined below:

    • white blood cells (wbc) count >= 3. 0 × 10\^9 per liter (/l)
    • absolute neutrophil count >= 1. 5 × 10\^9/l
    • lymphocyte count >= 0. 5 × 10\^9/l
    • platelet count >= 100 × 10\^9/l
    • hemoglobin >= 9 gram per deciliter (g/dl) (may had been transfused)

  • adequate hepatic function as defined below:

    • a total bilirubin level less than equals to (\<=) 1. 5 × upper limit of normal (uln) range
    • aspartate aminotransferase (ast) levels \<= 2. 5 × uln (≤ 3 × uln for expansion cohorts)
    • alanine aminotransferase (alt) levels \<= 2. 5 × uln (≤ 3 × uln for expansion cohorts)
    • subjects with documented gilbert disease were allowed if total bilirubin > 1. 5 but less than 3 × uln
  • adequate renal function as defined by an estimated creatinine clearance >= 50 milliliter per minute (ml/min) according to cockcroft-gault formula
  • negative blood pregnancy test at screening for women of childbearing potential. For purposes of this trial, women of childbearing potential were defined as all female subjects after puberty unless they were postmenopausal for at least 1 year, surgically sterile or sexually inactive.
  • highly effective contraception (ie, methods with a failure rate of less than 1% per year) must been used before started of treatment, for duration of trial treatment, and for at least 50 days after stopping studied treatment for both men and women if risk of conception exists. The effects of avelumab and m9241 on developing human fetus were unknown; thus, women of childbearing potential and men agreed to use highly effective contraception.

Part B:

  • Availability of a fresh tumor biopsy was mandatory for eligibility in the RCC cohort. The biopsy or surgical specimen should be collected within 28 days prior to the first IMP administration. If a subject had 2 separate biopsy attempts in which usable tissue was not obtained, enrollment would have been possible after discussion with the Medical Monitor. For other expansion cohorts, availability of either tumor archival material (\< 6 months old) or fresh biopsies (obtained within 28 days) was acceptable with one of these being mandatory. For formalin-fixed paraffin-embedded samples, either block or sections (> 15) provided. Tumor biopsies and tumor archival material should have been suitable for biomarker assessment - Locally advanced or metastatic UC that had progressed during or after at least one previous platinum-based chemotherapy and not previously treated with anti-PD-1/PD-L1 agents: Histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of urothelium(including renal pelvis, ureters, urinary bladder, and urethra). Participants must had progressed during or after treatment with at least 1 platinum-containing regimen for inoperable locally advanced or metastatic UC or disease recurrence. Participants who had received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing regimen were considered as second line. Participants with mixed histologies were required to have a dominant transitional cell pattern.
  • Non-small cell lung cancer (NSCLC), first-line metastatic: Stage IV (per seventh International Association for the Study of Lung Cancer classification) histologically confirmed NSCLC. Participants must not had received treatment for their metastatic disease. Participants could have received adjuvant chemotherapy or loco-regional treatment that included chemotherapy for locally advanced disease, as long as disease recurrence occurred at least 6 months after the completion of the last administration of chemotherapy. Only epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type were allowed (ie, EGFR mutation and ALK translocation / re arrangement excluded). Non squamous cell histologies and never / former light smoker (\< 15 pack years) squamous cell carcinoma Participants (per local standard of care) required testing if status was unknown. Participants must had low tumor PD-L1 expression defined as \< 50% tumor proportion score determined using PD-L1 IHC 22C3 pharmDx test or an equivalent Food and Drug Administration (FDA)- approved PD-L1 test. Availability of either tumor archival material or fresh biopsies within 28 days was acceptable with one of these being mandatory. For FFPE samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor archival material had been suitable for biomarker assessment. This cohort would not be opened for enrollment in Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom.
  • Colorectal cancer (CRC): Histologically or cytologically confirmed recurrent or refractory metastatic CRC (according to American Joint Committee on Cancer / International Union Against Cancer Tumor Node Metastasis [TNM] Staging System seventh edition) after failure of prior therapy containing oxaliplatin / fluoropyrimidine and / or irinotecan / fluoropyrimidine and, if eligible, cetuximab (Erbitux®) and bevacizumab (Avastin®). Only Participants with microsatellite instability (MSI)-low or microsatellite stable (MSS) metastatic CRC are eligible. Participants without existing MSI test results had MSI status performed locally by a Clinical Laboratory Improvement Amendments (CLIA)-certified IHC or polymerase chain reaction (PCR)-based test (PCR based MSI test is preferred). Participants had to be willing to undergo an on-treatment biopsy procedure. Availability of either tumor archival material or fresh biopsies within 28 days was acceptable with one of these being mandatory. For FFPE samples, either a block or sections (> 15) could be provided. Tumor biopsies and tumor archival material had to be suitable for biomarker assessment. For Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom, participants in the second-line setting had exhausted or were considered ineligible or intolerant (in the opinion of the Investigator) of available second-line chemotherapy options.
  • Renal cell carcinoma (RCC), primary immune checkpoint inhibitor failure: Histologically or cytologically documented metastatic RCC with a component of clear cell subtype. Participants must have had progressive disease (PD) within 6 months or best overall response of stable disease (SD) for ≥ 6 months following start of therapy with any antibody / drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) for advanced or metastatic disease (either as monotherapy or combination therapy, in any line). Fresh tumor biopsy was required for enrollment. If a subject had 2 separate biopsy attempts in which usable tissue was not obtained, enrollment could be possible after discussion with the Medical Monitor. Participants had to be willing to undergo an on-treatment biopsy procedure. In France, in addition to having received checkpoint inhibitor therapy, participants should have already received recommended local-standard therapy per discretion of the Investigator.

Exclusion criteria

Exclusion Criteria:

  • Concurrent treatment with a non-permitted drug/intervention (listed below)

    • Anticancer treatment (eg, cytoreductive therapy, radiotherapy, immune therapy, cytokine therapy, monoclonal antibody, targeted small molecule therapy) or any investigational drug within 4 weeks or 5 half-lives, whichever was shorter, prior to start of trial treatment, or not recovered from adverse event (AE) related to such therapies, with the following exceptions: Palliative radiotherapy delivered in a normal organ-sparing technique is permitted; Erythropoietin, darbepoetin-α and granulocyte colony-stimulating factor permitted; Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis permitted (i.e. luteinizing hormone-releasing hormone agonist/antagonists). No other hormonal anticancer therapy was permitted.
    • Major surgery (as deemed by Investigator) for any reason, except diagnostic biopsy, within 4 weeks prior to start of trial treatment, or not fully recovered from surgery within 4 weeks prior to start of trial treatment.
    • Participants receiving immunosuppressive agents (such as steroids) for any reason were tapered off these drugs before start of trial treatment, with following exceptions: Participants with adrenal insufficiency, continued corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily; Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) was permitted; Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon was acceptable as long as it was anticipated that the administration of steroids would be completed in 14 days, or that the dose after 14 days would be equivalent to \<= 10 mg prednisone daily.
  • Any prior treatment with any form of interlukin-12 (IL-12)
  • For the NSCLC, CRC, and UC expansion cohorts, prior therapy with any antibody / drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) antibody was prohibited.
  • Intolerance to checkpoint inhibitor therapy, as defined by the occurrence of an AE requiring drug discontinuation. - Active or history of primary or metastatic central nervous system tumors
  • Prior organ transplantation, including allogeneic stem-cell transplantation
  • Previous malignant disease (other than the indication for this trial) within the last 5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to trial entry and subject was deemed to have been cured with no additional therapy required or anticipated to be required.

  • Significant acute or chronic infections requiring systemic therapy including, among others:

    • History of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome • Hepatitis B or C infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV deoxy ribonucleic acid (DNA) or HBV core antibody positive alone with reflex to positive HBV DNA or positive hepatitis C virus [HCV] antibody with reflex to positive HCV ribonucleic acid [RNA]). Participants with history of infection must had polymerase chain reaction documentation that infection was cleared.
  • Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment wer eligible if they wer stable on other medical treatment and do not fulfill exclusion criterion including Uncontrolled intercurrent illness - Known severe hypersensitivity reactions to monoclonal antibodies (Grade>= 3 National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma)

  • History of allergic reaction to methotrexate (trace methotrexate may be present in M9241 as a part of manufacturing process) or history of severe hypersensitivity reaction to any other ingredient of study drug(s) and / or their excipients. Since M9241 contains sucrose as an excipient, participants suffering from hereditary fructose intolerance also excluded - Persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v4.03 with the following exceptions:

    • Neuropathy Grade \<= 2 was acceptable.
    • All grades of alopecia acceptable.
    • Endocrine dysfunction on replacement therapy was acceptable.
  • Pregnancy or lactation
  • Known alcohol or drug abuse as deemed by the Investigator

  • Uncontrolled intercurrent illness including, but not limited to:

    • Hypertension uncontrolled by standard therapies (not stabilized to 150/90 millimeter of mercury (mm Hg) or lower)
    • Uncontrolled active infection
    • Uncontrolled diabetes (eg, glycosylated hemoglobin [HgbA1c] >= 8%)
  • Clinically significant (or active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class >= II), or serious cardiac arrhythmia requiring medication
  • All other significant diseases (eg, inflammatory bowel disease, current severe acute or chronic colitis) or chronic medical conditions (including laboratory abnormalities) that in opinion of Investigator might impair subject's tolerance of trial treatment or interpretation of trial results.
  • Any psychiatric condition that would prohibit understanding or endering of informed consent or that would limit compliance with trial requirements.
  • Legal incapacity or limited legal capacity.
  • Administration of a live vaccine within 30 days prior to trial entry.
  • Any subject with possible area of ongoing necrosis (non-disease related), such as active ulcer, non-healing wound, or intercurrent bone fracture that may be at risk of delayed healing due to protocol therapy.
  • Oxygen saturation \< 90% at rest, known pulmonary fibrosis, or active interstitial lung disease.
  • History of congenital or active immunodeficiency, with exception of acquired treatment-related hypogammaglobulinemia requiring periodic IV immunoglobulin infusion.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
52 participants (actual)

Study arms

  • Experimental
    Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg

    Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.

    Drug: Avelumab · Drug: M9241 · Drug: M9241 (MTD)

  • Experimental
    Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg

    Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.

    Drug: Avelumab · Drug: M9241

  • Experimental
    Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg

    Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.

    Drug: Avelumab · Drug: M9241

  • Experimental
    Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg

    Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.

    Drug: Avelumab · Drug: M9241

  • Experimental
    Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg

    Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.

    Drug: Avelumab (Once weekly)

  • Experimental
    Part B Cohort 1: UC Cohort Stage 1 combination therapy

    Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study.

    Drug: Avelumab (Once weekly) · Drug: Avelumab (Expansion cohort)

Interventions

  • DrugAvelumab

    Participants received avelumab intravenous (IV) infusion once a week on Day 1 and Day 15 of each cycle.

    Also known as: MSB0010718C

  • DrugM9241

    Participants received Subcutaneous (SC) injection of M9241 in escalating doses on Day 1 of each cycle.

  • DrugAvelumab (Once weekly)

    Participants received avelumab once weekly in combination with M9241 every 4 weeks at M9241 maximum tolerated dose (MTD) for first 12 weeks followed by avelumab once every 2 weeks plus M9241 once every 4 weeks at M9241 MTD until a criterion for treatment discontinuation has been met.

  • DrugM9241 (MTD)

    Participants received M9241 at M9241 MTD once every 4 weeks until a criterion for treatment discontinuation has been met.

  • DrugAvelumab (Expansion cohort)

    Participants in the expansion cohorts received Induction Therapy (Avelumab once weekly + M9241 once every 4 weeks) through Cycle 3 (for 12 weeks) then starting at Cycle 4, Continuation Therapy (Avelumab once every 2 weeks + M9241 once every 4 weeks).

06

What researchers measure

Primary outcomes

  1. Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03

    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

    Time frame: From first dose of study treatment up to 1311 days

  2. Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03

    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

    Time frame: Part B: From first dose of study treatment up to 443 days

  3. Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

    AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported.

    Time frame: From first dose of study treatment up to 1311 days

  4. Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

    AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported.

    Time frame: First dose of study drug up to 443 days

  5. Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

    A DLT is any Grade (\>=) 3 non-hematologic AE or any Grade (\>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade \>=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to \<= Grade 2 within 7 days of initiating therapy will be a DLT. Any Grade 4 neutropenia of \< 5 days duration; Grade 3 infusion-related reaction resolving within 6 hours of infusion; Grade 3 diarrhea or skin toxicity that resolves to Grade \<= 1 within 7 days after medical management; Transient Grade 3 fatigue, local reactions, flu-like symptoms; Tumor flare phenomenon of known or suspected tumor did not consider a DLT.

    Time frame: Time from first treatment to final assessment up to 3 weeks

  6. Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Not evaluable (NE): No post-baseline assessment. BOR assessments were assessed by investigators.

    Time frame: First dose of study drug up to 443 days

Secondary outcomes

  1. Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab

    Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

    Time frame: Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  2. Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab

    The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  3. Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab

    Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  4. Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab

    Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  5. Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab

    Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  6. Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab

    Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  7. Part A: Apparent Terminal Half-life (t1/2) of Avelumab

    Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  8. Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab

    AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

    Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

  9. Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241

    Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). (AUC0-t) was calculated according to the mixed log-linear trapezoidal rule.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  10. Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241

    The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  11. Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241

    Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  12. Part A: Maximum Observed Serum Concentration (Cmax) of M9241

    Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  13. Part A: Minimum Observed Serum Concentration (Cmin) of M9241

    Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  14. Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241

    Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  15. Part A: Apparent Terminal Half-life (t1/2) of M9241

    Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  16. Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241

    AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

    Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)

  17. Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241

    ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples).

    Time frame: First dose of study drug up to 1311 days

  18. Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1

    BOR is defined as best response of any of confirmed complete response, confirmed partial response, stable disease and progressive disease recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Non-CR/non-PD (for participants with non-measurable disease at baseline) = at least one Non-CR/non-PD assessment (or better) \>= 6 weeks after first study treatment administration and before progression and Not Evaluable: all other cases. BOR assessments were assessed by investigators.

    Time frame: First dose of study drug up to 1311 days

  19. Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1

    BOR: best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to \[\>=\] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.

    Time frame: First dose of study drug up to 1311 days

  20. Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator

    PFS was defined as the time from first treatment day until date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier estimates.

    Time frame: Time from first dose administration until progressive disease or death, assessed up to 443 days

  21. Part B: Overall Survival (OS) Time

    The OS time was defined as the time from treatment day 1 to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier estimates.

    Time frame: Time from first dose of study treatment up to 443 days

  22. Part B: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator

    DOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. If a participant has not an event (PD or death), DOR was censored at the date of last adequate tumor assessment.

    Time frame: Time from first dose of study treatment up to 443 days

  23. Part B: Maximum Observed Serum Concentration (Cmax) of M9241

    Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

    Time frame: Pre-dose, 1 hour post-dose on Day 1 and Day 29 of Cycle 1 and 2 (Each cycle: 28 days)

  24. Part B: Serum Trough Concentration Levels (Ctrough) of M9241

    Ctrough was defined as the trough or minimum serum concentration.

    Time frame: Pre-dose, 1 hour post-dose on Day 1 of cycle 2; Day 1, 27 of cycle 3; Day 1 of cycle 5 (Each cycle: 28 days)

  25. Part B: Concentration at the End of Infusion (Ceoi) of Avelumab

    Ceoi is the observed serum drug concentration at the end of Intravenous (IV) infusion.

    Time frame: Pre-dose, 1 hour post-dose on Day 1 and 15 of Cycle 1 and 2 (Each cycle: 28 days)

  26. Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab

    Ctrough was defined as the trough or minimum serum concentration.

    Time frame: Pre-dose, 1 hour post-dose on Day 15, 29 and 43

  27. Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241

    ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples).

    Time frame: Time from first dose of study treatment up to 443 days

07

Results

Posted Sep 20, 2024
Limitations and caveats
The study was terminated due to pre-specified futility criteria met.

Participant flow

The study consisted of 2 parts: Part A (Dose escalation) and Part B (Dose expansion).

Participant flow — Overall Study
MilestonePart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental)Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental)Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Started9776716
Completed9776716
Not completed000000

Outcome measures

PrimaryPart A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

Time frame:
From first dose of study treatment up to 1311 days
Reported as:
Count of participants · Participants
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03
ParticipantsPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Participants with TEAEs97767
Participants with Treatment-related-TEAEs85656
PrimaryPart B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

Time frame:
Part B: From first dose of study treatment up to 443 days
Reported as:
Count of participants · Participants
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03
ParticipantsPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Participants with TEAEs16
Participants with Treatment-Related AEs15
PrimaryPart A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported.

Time frame:
From first dose of study treatment up to 1311 days
Reported as:
Count of participants · Participants
Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
ParticipantsPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Grade >=365644
Grade >=422221
Grade 501011
PrimaryPart B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported.

Time frame:
First dose of study drug up to 443 days
Reported as:
Count of participants · Participants
Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
ParticipantsPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Any Grade15
Grade >=38
Grade >=41
Grade 50
PrimaryPart A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

A DLT is any Grade (\>=) 3 non-hematologic AE or any Grade (\>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade \>=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to \<= Grade 2 within 7 days of initiating therapy will be a DLT. Any Grade 4 neutropenia of \< 5 days duration; Grade 3 infusion-related reaction resolving within 6 hours of infusion; Grade 3 diarrhea or skin toxicity that resolves to Grade \<= 1 within 7 days after medical management; Transient Grade 3 fatigue, local reactions, flu-like symptoms; Tumor flare phenomenon of known or suspected tumor did not consider a DLT.

Time frame:
Time from first treatment to final assessment up to 3 weeks
Reported as:
Count of participants · Participants
Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
ParticipantsPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)00100
PrimaryPart B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Not evaluable (NE): No post-baseline assessment. BOR assessments were assessed by investigators.

Time frame:
First dose of study drug up to 443 days
Reported as:
Count of participants · Participants
Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ParticipantsPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Complete Response0
Partial Response0
Stable Disease2
Progressive Disease13
Not evaluable1
SecondaryPart A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab

Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Time frame:
Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Geometric mean · microgram*hour per milliliter (mcg*h/mL)
Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab
microgram*hour per milliliter (mcg*h/mL)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 120700 ± 38.126600 ± 57.923600 ± 16.617400 ± 33.417900 ± 39.7
Cycle 1 Day 1522800 ± 40.526100 ± 42.528300 ± 39.422000 ± 19.2—
Cycle 1 Day 22————26300 ± 31.0
Cycle 2 Day 126400 ± 17.227900 ± 47.922700 ± 23.222700 ± 10.522100 ± 42.7
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab

The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Geometric mean · microgram*hour per milliliter (mcg*h/mL)
Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab
microgram*hour per milliliter (mcg*h/mL)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 122300 ± 41.530100 ± 75.826500 ± 21.518800 ± 29.527000 ± 65.0
Cycle 1 Day 1526300 ± 37.229800 ± 35.727100 ± 34.523000 ± 26.0—
Cycle 1 Day 22————43400 ± 56.1
Cycle 2 Day 129800 ± 18.433100 ± 48.424300 ± 30.624400 ± 13.335100 ± 40.3
SecondaryPart A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab

Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Geometric mean · One per hour (1/hour)
Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab
One per hour (1/hour)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 10.00847 ± 29.60.00729 ± 48.50.00756 ± 20.60.00790 ± 14.40.00822 ± 37.1
Cycle 1 Day 150.00780 ± 31.60.00814 ± 15.70.00780 ± 31.40.00803 ± 17.1—
Cycle 1 Day 22————0.00620 ± 34.3
Cycle 2 Day 10.00659 ± 15.70.00714 ± 39.80.00868 ± 19.20.00830 ± 16.40.00793 ± 35.9
SecondaryPart A: Maximum Observed Serum Concentration (Cmax) of Avelumab

Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Geometric mean · microgram/milliliter (mcg/mL)
Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab
microgram/milliliter (mcg/mL)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1241 ± 39.9244 ± 29.9287 ± 36.4156 ± 67.7228 ± 29.3
Cycle 1 Day 15229 ± 54.4250 ± 14.6256 ± 32.0201 ± 25.6—
Cycle 1 Day 22————269 ± 44.0
Cycle 2 Day 1213 ± 21.3249 ± 37.5210 ± 19.7200 ± 8.1318 ± 33.5
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Minimum Observed Serum Concentration (Cmin) of Avelumab

Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Geometric mean · mcg/mL
Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab
mcg/mLPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1511.3 ± 90.414.5 ± 37.214.0 ± 70.39.28 ± 51.8—
Cycle 1 Day 22————74.1 ± 62.0
Cycle 2 Day 120.5 ± 37.624.0 ± 79.914.4 ± 91.913.1 ± 24.459.3 ± 122.5
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab

Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Median · hours
Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab
hoursPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 14.00 (1.00 to 25.08)1.05 (1.00 to 9.00)3.90 (1.00 to 4.25)2.58 (1.00 to 44.78)4.00 (1.00 to 22.20)
Cycle 1 Day 155.04 (1.00 to 48.42)1.13 (1.00 to 25.72)4.00 (1.22 to 49.00)4.09 (1.03 to 29.18)—
Cycle 1 Day 22————4.00 (1.00 to 43.03)
Cycle 2 Day 11.58 (1.13 to 25.00)1.17 (1.10 to 4.08)23.07 (3.98 to 25.00)2.00 (1.00 to 25.35)4.00 (1.12 to 9.00)
Cycle 4 Day 1————NA (NA to NA)
SecondaryPart A: Apparent Terminal Half-life (t1/2) of Avelumab

Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Median · hours
Part A: Apparent Terminal Half-life (t1/2) of Avelumab
hoursPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 194.7 (48.4 to 108)87.4 (50.2 to 223)95.2 (70.1 to 123)87.1 (69.4 to 106)70.5 (60.2 to 148)
Cycle 1 Day 15101 (54.9 to 115)77.6 (75.0 to 103)84.1 (65.0 to 136)86.7 (69.9 to 106)—
Cycle 1 Day 22————102 (83.3 to 180)
Cycle 2 Day 1106 (88.5 to 125)94.9 (68.6 to 173)80.7 (67.5 to 95.1)86.2 (67.0 to 98.1)81.1 (55.9 to 138)
SecondaryPart A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab

AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame:
PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Reported as:
Geometric mean · mcg*h/mL
Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab
mcg*h/mLPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 120900 ± 37.626700 ± 58.324500 ± 19.217400 ± 33.119800 ± 44.7
Cycle 1 Day 1524100 ± 35.027600 ± 33.128300 ± 39.421400 ± 24.2—
Cycle 1 Day 22————27500 ± 34.7
Cycle 2 Day 126400 ± 17.429500 ± 37.622900 ± 27.122800 ± 11.625500 ± 26.1
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241

Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). (AUC0-t) was calculated according to the mixed log-linear trapezoidal rule.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Geometric mean · nanogram*hour/milliliter (ng*h/mL)
Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241
nanogram*hour/milliliter (ng*h/mL)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1105 ± 114.4421 ± 82.9661 ± 58.2621 ± 96.5873 ± 264.0
Cycle 2 Day 1183 ± 151.7306 ± 132.6184 ± 174.01250 ± 46.21060 ± 308.8
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241

The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Geometric mean · ng*h/mL
Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241
ng*h/mLPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1—NA ± NANA ± NANA ± NA2370 ± 31.5
Cycle 2 Day 1—NA ± NA—NA ± NA2860 ± 19.9
SecondaryPart A: Terminal Elimination Rate Constant (Lambdaz) of M9241

Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Geometric mean · One per hour (1/hour)
Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241
One per hour (1/hour)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1—NA ± NANA ± NANA ± NA0.00451 ± 12.5
Cycle 2 Day 1—NA ± NA—NA ± NA0.00835 ± 14.0
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Maximum Observed Serum Concentration (Cmax) of M9241

Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Geometric mean · ng/mL
Part A: Maximum Observed Serum Concentration (Cmax) of M9241
ng/mLPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 12.79 ± 79.14.42 ± 84.912.6 ± 40.95.91 ± 54.86.88 ± 99.6
Cycle 2 Day 12.68 ± 45.73.81 ± 39.44.45 ± 112.89.42 ± 63.310.4 ± 134.1
Cycle 4 Day 1————NA ± NA
SecondaryPart A: Minimum Observed Serum Concentration (Cmin) of M9241

Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Mean · ng/mL
Part A: Minimum Observed Serum Concentration (Cmin) of M9241
ng/mLPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 2 Day 10.0 ± 0.00.0 ± 0.00.0 ± 0.00.0 ± 0.00.0 ± 0.0
SecondaryPart A: Time to Reach Maximum Observed Concentration (Tmax) of M9241

Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Median · hours
Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241
hoursPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 125.08 (24.58 to 26.05)25.17 (3.17 to 240.73)24.11 (9.02 to 42.73)36.17 (9.17 to 238.62)25.08 (19.03 to 46.40)
Cycle 2 Day 134.28 (9.33 to 44.45)25.17 (10.13 to 45.03)25.08 (9.27 to 47.88)25.43 (10.10 to 94.93)25.50 (9.35 to 168.18)
Cycle 4 Day 1————NA (NA to NA)
SecondaryPart A: Apparent Terminal Half-life (t1/2) of M9241

Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Median · hours
Part A: Apparent Terminal Half-life (t1/2) of M9241
hoursPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1—NA (NA to NA)NA (NA to NA)NA (NA to NA)161 (128 to 169)
Cycle 2 Day 1—NA (NA to NA)—NA (NA to NA)84.4 (71.6 to 94.6)
SecondaryPart A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241

AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame:
PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Reported as:
Geometric mean · ng*h/mL
Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241
ng*h/mLPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Cycle 1 Day 1—NA ± NANA ± NA835 ± 64.32130 ± 35.6
Cycle 2 Day 1—NA ± NANA ± NANA ± NA2390 ± 80.4
SecondaryPart A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241

ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples).

Time frame:
First dose of study drug up to 1311 days
Reported as:
Count of participants · Participants
Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241
ParticipantsPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Avelumab: ADA pre-existing00001
Avelumab: ADA Treatment boosted00000
Avelumab: Treatment-Emergent Transient positive00110
Avelumab: Treatment-Emergent Persistent Positive01101
M9241: ADA pre-existing00000
M9241: ADA Treatment boosted00000
M9241: Treatment-Emergent Transient Positive00000
M9241: Treatment-Emergent Persistent Positive00001
SecondaryPart A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1

BOR is defined as best response of any of confirmed complete response, confirmed partial response, stable disease and progressive disease recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Non-CR/non-PD (for participants with non-measurable disease at baseline) = at least one Non-CR/non-PD assessment (or better) \>= 6 weeks after first study treatment administration and before progression and Not Evaluable: all other cases. BOR assessments were assessed by investigators.

Time frame:
First dose of study drug up to 1311 days
Reported as:
Count of participants · Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1
ParticipantsPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Complete Response (CR)01010
Partial Response (PR)00000
Stable Disease (SD)22212
Progressive Disease (PD)63425
Non CR/Non PD00000
Not Evaluable11120
SecondaryPat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1

BOR: best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to \[\>=\] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.

Time frame:
First dose of study drug up to 1311 days
Reported as:
Count of participants · Participants
Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1
ParticipantsPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kgPart A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg
Immune-Related Complete Response (irCR)01010
Immune-Related Partial Response (irPR)00000
Immune-Related Stable Disease (irSD)22233
Immune-Related Progressive Disease (irPD)00002
Not evaluable (NE)74522
SecondaryPart B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator

PFS was defined as the time from first treatment day until date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier estimates.

Time frame:
Time from first dose administration until progressive disease or death, assessed up to 443 days
Reported as:
Median · weeks
Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator
weeksPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator7.6 ± 7.1
SecondaryPart B: Overall Survival (OS) Time

The OS time was defined as the time from treatment day 1 to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier estimates.

Time frame:
Time from first dose of study treatment up to 443 days
Reported as:
Median · months
Part B: Overall Survival (OS) Time
monthsPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Part B: Overall Survival (OS) Time4.9 ± 2.3
SecondaryPart B: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator

DOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. If a participant has not an event (PD or death), DOR was censored at the date of last adequate tumor assessment.

Time frame:
Time from first dose of study treatment up to 443 days

No measurements were reported for this outcome.

SecondaryPart B: Maximum Observed Serum Concentration (Cmax) of M9241

Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

Time frame:
Pre-dose, 1 hour post-dose on Day 1 and Day 29 of Cycle 1 and 2 (Each cycle: 28 days)
Reported as:
Geometric mean · ng/mL
Part B: Maximum Observed Serum Concentration (Cmax) of M9241
ng/mLPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Day 16.95 ± 59.6
Day 297.62 ± 113.0
SecondaryPart B: Serum Trough Concentration Levels (Ctrough) of M9241

Ctrough was defined as the trough or minimum serum concentration.

Time frame:
Pre-dose, 1 hour post-dose on Day 1 of cycle 2; Day 1, 27 of cycle 3; Day 1 of cycle 5 (Each cycle: 28 days)
Reported as:
Mean · ng/mL
Part B: Serum Trough Concentration Levels (Ctrough) of M9241
ng/mLPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Day 290 ± 0
Day 570 ± 0
Day 83NA ± NA
Day 113NA ± NA
SecondaryPart B: Concentration at the End of Infusion (Ceoi) of Avelumab

Ceoi is the observed serum drug concentration at the end of Intravenous (IV) infusion.

Time frame:
Pre-dose, 1 hour post-dose on Day 1 and 15 of Cycle 1 and 2 (Each cycle: 28 days)
Reported as:
Geometric mean · mcg/mL
Part B: Concentration at the End of Infusion (Ceoi) of Avelumab
mcg/mLPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Day 1199 ± 22.0
Day 15220 ± 37.9
Day 29272 ± 59.6
Day 43253 ± 40.0
SecondaryPart B: Serum Trough Concentration Levels (Ctrough) of Avelumab

Ctrough was defined as the trough or minimum serum concentration.

Time frame:
Pre-dose, 1 hour post-dose on Day 15, 29 and 43
Reported as:
Geometric mean · mcg/mL
Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab
mcg/mLPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Day 1554.2 ± 64.9
Day 2953.9 ± 217.5
Day 4344.6 ± 101.8
SecondaryPart B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241

ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples).

Time frame:
Time from first dose of study treatment up to 443 days
Reported as:
Count of participants · Participants
Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241
ParticipantsPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Avelumab: ADA pre-existing0
Avelumab: ADA treatment boosted0
Avelumab: Treatment-Emergent Transient Positive0
Avelumab: Treatment-Emergent Persistent Positive1
M9241: ADA pre-existing0
M9241: ADA treatment boosted0
M9241: Treatment-Emergent Transient Positive1
M9241: Treatment-Emergent Persistent Positive0

Adverse events

Collected over Part A: Baseline up to 1311 days Part B: Baseline up to 443 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)9/9 (100%)4/9 (44.4%)9/9 (100%)
Part A Cohort 2: M9241 8 mcg/kg +Avelumab 10 mg/kg5/7 (71.4%)4/7 (57.1%)7/7 (100%)
Part A Cohort 3: M9241 12 mcg/kg +Avelumab 10 mg/kg6/7 (85.7%)3/7 (42.9%)7/7 (100%)
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg5/6 (83.3%)3/6 (50%)6/6 (100%)
Part A Cohort 5: M9241 16.8 mcg/kg +Avelumab 800 mg7/7 (100%)4/7 (57.1%)7/7 (100%)
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)12/16 (75%)12/16 (75%)16/16 (100%)
Most frequent serious events
Showing 10 of 41
Most frequent serious events
EventPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg +Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg +Avelumab 800 mgPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
Disease progressionGeneral disorders0/91/70/71/61/74/16
PyrexiaGeneral disorders0/90/70/70/60/73/16
Large intestinal obstructionGastrointestinal disorders0/90/70/71/60/70/16
Cytokine release syndromeImmune system disorders0/90/70/71/60/70/16
Device related infectionInfections and infestations0/90/70/71/60/70/16
AnaemiaBlood and lymphatic system disorders0/90/70/70/61/71/16
Autoimmune haemolytic anaemiaBlood and lymphatic system disorders0/90/70/70/61/70/16
Retroperitoneal haemorrhageGastrointestinal disorders0/91/70/70/60/70/16
Gallbladder obstructionHepatobiliary disorders0/90/70/70/61/70/16
Immune-mediated hepatitisHepatobiliary disorders0/90/71/70/60/70/16
Most frequent other events
Showing 10 of 179
Most frequent other events
EventPart A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 3: M9241 12 mcg/kg +Avelumab 10 mg/kgPart A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kgPart A Cohort 5: M9241 16.8 mcg/kg +Avelumab 800 mgPart B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)
FatigueGeneral disorders7/93/74/72/64/70/16
AnaemiaBlood and lymphatic system disorders3/94/75/74/63/78/16
NauseaGastrointestinal disorders1/92/72/74/65/77/16
PyrexiaGeneral disorders6/95/73/74/64/710/16
Lymphocyte count decreasedInvestigations4/94/73/74/63/70/16
Influenza like illnessGeneral disorders4/94/72/73/60/70/16
Decreased appetiteMetabolism and nutrition disorders1/92/71/73/64/74/16
HypophosphataemiaMetabolism and nutrition disorders0/90/71/72/64/71/16
VomitingGastrointestinal disorders2/92/70/73/62/74/16
Blood creatinine increasedInvestigations0/91/71/73/60/70/16

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental)Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental)Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)Total
<=18 years0000000
Between 18 and 65 years64455832
>=65 years33312820
Sex: Female, Male
Sex: Female, Male(Participants)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental)Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental)Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)Total
Female52322418
Male454451234
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental)Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental)Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)Total
Hispanic or Latino0000202
Not Hispanic or Latino867651648
Unknown or Not Reported1100002
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental)Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental)Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental)Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)Total
American Indian or Alaska Native0000000
Asian1000001
Native Hawaiian or Other Pacific Islander0000000
Black or African American0110103
White75666838
More than one race0000000
Unknown or Not Reported11000810
08

Study locations

33 sites
  • California Cancer Associates for Research & Excellence, Inc.
    San Diego, California 92111, United States
  • Sharp Memorial Hospital
    San Diego, California 92123, United States
  • St Joseph Heritage Healthcare
    Santa Rosa, California 95403, United States
  • Yale University Institutional Review Board
    New Haven, Connecticut 06520, United States
  • Holy Cross Hospital Inc.
    Fort Lauderdale, Florida 33308, United States
  • Hematology - Oncology Associates of the Treasure Coast
    Port Saint Lucie, Florida 34952, United States
  • Metairie Oncologists, LLC
    Metairie, Louisiana 70006, United States
  • National Cancer Institute
    Bethesda, Maryland 20892, United States
  • Virginia Piper Cancer Institute
    Minneapolis, Minnesota 55407, United States
  • Washington University
    Saint Louis, Missouri 63110, United States
  • UC Health, LLC.
    Cincinnati, Ohio 45229, United States
  • University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma 73104, United States
  • Cedar Sinai Medical Center
    Ashland, Oregon 97520, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Mary Crowley Cancer Research Centers
    Dallas, Texas 75251, United States
  • University of Vermont Medical Center
    Burlington, Vermont 05405, United States
  • Northwest Medical Specialties, PLLC
    Tacoma, Washington 98405, United States
  • Centre Hospitalier de l'Ardenne - Pharmacie
    Libramont, Belgium
  • GZA Ziekenhuizen - Campus Sint-Augustinus
    Wilrijk, Belgium
  • CHU Bordeaux - Hôpital Saint André
    Bordeaux cedex, France
  • Centre Georges François Leclerc
    Dijon cedex, France
  • Centre Oscar Lambret
    Lille cedex, France
  • Hôpital de la Timone# - CPCEM CIC - Bat F 1er étage
    Marseille cedex 5, France
  • Centre Hospitalier Lyon Sud
    Pierre Benite cedex, France
  • Centre Paul Strauss
    Strasbourg Cedex, France
  • Orszagos Onkologiai Intezet
    Budapest, Hungary
  • Fondazione IRCCS Istituto Nazionale dei Tumori
    Milano, Italy
  • IOV - Istituto Oncologico Veneto IRCCS
    Padova, Italy
  • A.O.U. Senese Policlinico Santa Maria alle Scotte
    Siena, Italy
  • Amsterdam UMC, Locatie VUMC
    Amsterdam, Netherlands
  • Antoni van Leeuwenhoek Ziekenhuis
    Amsterdam, Netherlands
  • Maastricht University Medical Center
    Maastricht, Netherlands
  • Hospital Universitario Virgen del Rocio
    Sevilla, Spain
09

References and documents

Publications

  • Strauss J, Deville JL, Sznol M, Ravaud A, Maruzzo M, Pachynski RK, Gourdin TS, Maio M, Dirix L, Schlom J, Donahue RN, Tsai YT, Wang X, Vugmeyster Y, Beier F, Seebeck J, Schroeder A, Chennoufi S, Gulley JL. First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma. J Immunother Cancer. 2023 May;11(5):e005813. doi: 10.1136/jitc-2022-005813. PubMed 37236636 ↗

Study documents

  • Study protocol · Jul 22, 2019
  • Statistical analysis plan · Oct 20, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02994953
Lead sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
Responsible party
Sponsor
First posted
Dec 16, 2016
Start date
Jan 31, 2017
Primary completion
Oct 8, 2020
Completion
Oct 8, 2020
Results posted
Sep 20, 2024
Last update
Sep 20, 2024

Study contacts

Medical Responsible
study director · EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in May 2024. You cannot join it, but the record below documents what was studied.

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