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CompletedNCT02517398Updated May 3, 2024Results posted

MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors

A Phase 1 interventional study of MSB0011359C in Solid Tumors, sponsored by EMD Serono Research & Development Institute, Inc.. Completed at 118 sites in 12 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-05-03.

Sponsored by EMD Serono Research & Development Institute, Inc. (part of Merck KGaA, Darmstadt, Germany) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
600
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The main purpose of this Phase I study was to test MSB0011359C (M7824) at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Phase I means the study drug has not previously been given to humans or has only been given to a limited number of people, although it has been extensively studied in animals. Based on this information, it is hoped to find out which dose could be best for the treatment of patients. There are two parts of this research study: a dose-escalation part and an expansion part. Dose escalation means that the first people taking part in the study will receive low doses of the study drug, and as more people take part, the additional participants will receive a higher dose. This is done to find the safest dose for the study drug. Expansion means that after the dose-escalation part of the study has looked at the safety and effectiveness of different doses, many more people will be invited to take part in the study and will receive the study drug at the safest dose. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

Read the detailed description

This is a Phase I, open-label, dose-escalation trial with consecutive parallel-group expansion in selected solid tumor indications. The current trial wascomposed of a standard dose escalation "3 + 3" cohort design, for which 3 to 6 subjects will be enrolled at each dose level depending on the occurrence of dose limiting toxicities (DLTs), followed by a consecutive parallel-group expansion in selected solid tumor in dications. Cohorts of 3 subjects with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or standard therapy has failed, will receive MSB0011359C (M7824) at escalating dose levels. After determination of the Maximum tolerated dose (MTD), enrollment in several expansion cohorts will be opened to determine the safety, pharmacokinetic (PK) / Pharmacodynamic, and clinical activity of MSB0011359C (M7824). Subjects who have experienced a confirmed complete response (CR) should continue treatment through the end of 12 months, although additional treatment is possible. In the case of progressive disease (PD), subjects should continue treatment through their next tumor assessment. Additional indications will be planned based on emerging data in the field.

02

Conditions studied

  • Solid Tumors

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Keywords

  • Solid tumor
  • MSB0011359C (M7824)
  • Metastatic or Locally Advanced Solid Tumors
  • Bintrafusp alfa
  • INTR@PID
03

In context

Neoplasm Metastasis

3,562 studies on the registry are indexed under Neoplasm Metastasis; 875 are open to participants now.

This study's enrollment of 600 is above the median of 54 across 2,800 interventional studies indexed under Neoplasm Metastasis.

Browse Neoplasm Metastasis studies →

Lead sponsor

EMD Serono Research & Development Institute, Inc. is the lead sponsor of 87 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.

First submitted after EMD Serono Research & Development Institute, Inc. became part of Merck KGaA, Darmstadt, Germany.

Browse EMD Serono Research & Development Institute, Inc. studies →All Merck KGaA, Darmstadt, Germany studies →

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Ability to understand the purpose of the study, provide signed and dated informed consent, and able to comply with all procedures
  • In Japan, if a subject is \< 20 years, the written informed consent from his/her parent or guardian will be required in addition to the subject's written consent
  • Male or female subjects aged greater than or equal to (>=) 18 years
  • Life expectancy >= 12 weeks as judged by the Investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry
  • Disease must be measurable with at least 1 uni dimensional measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • Effective contraception for both male and female subjects if the risk of conception exists

Other protocol-defined inclusion criteria could apply.

Exclusion criteria

Exclusion Criteria:

  • Concurrent treatment with non-permitted drugs and other interventions
  • Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative radiotherapy delivered in a normal organ-spearing technique), immune therapy, or cytokine therapy
  • Major surgery within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted)
  • Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment
  • Previous malignant disease (other than the target malignancy to be investigated in this trial) within the last 3 years. Subjects with history of cervical carcinoma in situ, superficial or non invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent are NOT excluded. Subjects with other localized malignancies treated with curative intent need to be discussed with the Medical Monitor.
  • Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures
  • Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded
  • Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (eg, corneal transplant, hair transplant)

Other protocol-defined exclusion criteria could apply

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
600 participants (actual)

Study arms

  • Experimental
    MSB0011359C (M7824)

    Drug: MSB0011359C

Interventions

  • DrugMSB0011359C

    Subjects would receive intravenous infusion of MSB0011359C once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.

    Also known as: M7824

06

What researchers measure

Primary outcomes

  1. Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

    Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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.

    Time frame: From start of study drug administration up to 139 weeks

  2. Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death

    Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants With treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

    Time frame: From start of study drug administration up to 139 weeks

  3. Number of Participants With TEAEs and Related TEAEs Based on Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03

    AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade greater than or equal to (\>=) 3 and Grade \>=4 were reported.

    Time frame: From start of study drug administration up to 139 weeks

  4. Dose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03

    A DLT was defined as any grade \>= 3 Adverse Event (AE) suspected to be related to IMP by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment. According to the NCI-CTCAE, v4.03, occurring in the DLT evaluation period and assessed to be related to study treatment by the Investigator and / or Sponsor confirmed by the safety monitoring committee to be relevant for the study treatment.

    Time frame: From start of study drug administration up to 21 days

  5. Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC)

    BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Independent Endpoint Review Committee (IRC). BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

    Time frame: From date of randomization up to Week 66

  6. Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma

    DCR is defined as the percentage of participants with a confirmed CR+PR+SD+ Non-CR/non-PD at any time as per RANO criteria. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the RANO criteria. CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

    Time frame: From date of randomization up to Week 66

Secondary outcomes

  1. Maximum Concentration (Cmax) of M7824 in Plasma

    Cmax was obtained directly from the concentration versus time curve.

    Time frame: 0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

  2. Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824

    Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).

    Time frame: 0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose post-dose

  3. Apparent Terminal Half Life (t1/2) of M7824

    Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (\*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

    Time frame: Pre-dose, 0, 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

  4. Trough Plasma Concentration (Ctrough) of M7824

    Ctrough is the plasma concentration of a drug prior to administration.

    Time frame: 0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

  5. Apparent Plasma Clearance (CL) of M7824

    CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.

    Time frame: 0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

  6. Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824

    The detection of antibodies to M7824 was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive ADA of M7824 were reported.

    Time frame: Predose, up to Week 52

  7. Number of Participants With Best Overall Response (BOR) as Assessed by Investigator

    BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Investigator. BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

    Time frame: From date of randomization up to Week 66

  8. Dose Expansion: Number of Participants With TEAEs and Serious TEAEs

    An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. TEAEs were defined as events with onset date or worsening during the on-treatment period. Serious Adverse Event (SAE) was 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. Any TEAE included participants with both serious and non-serious AEs.

    Time frame: From start of study drug administration up to 200 weeks

  9. Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death

    Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants with treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

    Time frame: From start of study drug administration up to 200 weeks

  10. Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03

    AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade \>= 3 and Grade \>=4 TEAEs were reported.

    Time frame: From start of study drug administration up to 200 weeks

07

Results

Posted May 3, 2024

Participant flow

Participant flow — Overall Study
MilestoneDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Started33436107363868328336303233353215404041
Completed1000323101084321225654718
Not completed2343384262860288034293031302610363323
Withdrew: Death234238326245325732926232625227263020
Withdrew: Other00010000010001011001000
Withdrew: Lost to follow-up00000000010220110310102
Withdrew: Withdrew consent00000010027154254232931

Outcome measures

PrimaryDose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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.

Time frame:
From start of study drug administration up to 139 weeks
Reported as:
Count of participants · Participants
Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
ParticipantsDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kg
Participants with TEAEs3343610736
Participants with Serious TEAEs222118321
PrimaryDose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death

Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants With treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

Time frame:
From start of study drug administration up to 139 weeks
Reported as:
Count of participants · Participants
Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death
ParticipantsDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kg
Treatment-related TEAEs202256724
Treatment-related serious TEAEs000113110
Treatment-related TEAE leading to death000000000
PrimaryNumber of Participants With TEAEs and Related TEAEs Based on Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03

AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade greater than or equal to (\>=) 3 and Grade \>=4 were reported.

Time frame:
From start of study drug administration up to 139 weeks
Reported as:
Count of participants · Participants
Number of Participants With TEAEs and Related TEAEs Based on Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03
ParticipantsDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kg
Grade >= 3 TEAE332147526
Grade >= 4 TEAE002012001
Treatment-related Grade >= 3 TEAE000124200
Treatment-related Grade >= 4 TEAE000010000
PrimaryDose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03

A DLT was defined as any grade \>= 3 Adverse Event (AE) suspected to be related to IMP by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment. According to the NCI-CTCAE, v4.03, occurring in the DLT evaluation period and assessed to be related to study treatment by the Investigator and / or Sponsor confirmed by the safety monitoring committee to be relevant for the study treatment.

Time frame:
From start of study drug administration up to 21 days
Reported as:
Count of participants · Participants
Dose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03
ParticipantsDose-escalation: M7824 1 mg/kgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/Infusion
Dose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03000100
PrimaryDose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC)

BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Independent Endpoint Review Committee (IRC). BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

Time frame:
From date of randomization up to Week 66
Reported as:
Count of participants · Participants
Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC)
ParticipantsDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Complete response (CR)00000001000000
Partial response (PR)46231612242795
PrimaryDose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma

DCR is defined as the percentage of participants with a confirmed CR+PR+SD+ Non-CR/non-PD at any time as per RANO criteria. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the RANO criteria. CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Time frame:
From date of randomization up to Week 66
Reported as:
Number · Percentage of participants
Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma
Percentage of participantsDose-expansion: Glioblastoma
Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma22.9 (10.4 to 40.1)
SecondaryMaximum Concentration (Cmax) of M7824 in Plasma

Cmax was obtained directly from the concentration versus time curve.

Time frame:
0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Reported as:
Geometric mean · micrograms per milliliter (mcg/ml)
Maximum Concentration (Cmax) of M7824 in Plasma
micrograms per milliliter (mcg/ml)Dose-escalation: M7824 0.3 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-expansion: All Solid Tumors 1200mgDose-expansion: NSCLC-2L 500 mg
Maximum Concentration (Cmax) of M7824 in Plasma7.08 ± 9.122.5 ± 44.292.8 ± 74.8233 ± 9.1503 ± 15.7766 ± 8.0943 ± 19.7411 ± 28.5185 ± 39.7
SecondaryArea Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).

Time frame:
0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose post-dose
Reported as:
Geometric mean · hour*microgram per milliliter (h*mcg/ml)
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824
hour*microgram per milliliter (h*mcg/ml)Dose-escalation: M7824 0.3 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-expansion: All Solid Tumors 1200mgDose-expansion: NSCLC-2L 500 mg
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824747 ± 25.03170 ± 38.611000 ± 33.632600 ± 10.162200 ± 31.2114000 ± 9.1144000 ± 14.360300 ± 27.624900 ± 33.7
SecondaryApparent Terminal Half Life (t1/2) of M7824

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (\*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Time frame:
Pre-dose, 0, 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Reported as:
Geometric mean · Hour
Apparent Terminal Half Life (t1/2) of M7824
HourDose-escalation: M7824 0.3 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-expansion: All Solid Tumors 1200mgDose-expansion: NSCLC-2L 500 mg
Apparent Terminal Half Life (t1/2) of M782474.0 ± 20.9120 ± 16.9125 ± 22.6160 ± 23.0172 ± 30.3171 ± 31.5177 ± 15.8152 ± 23.3145 ± 23.5
SecondaryTrough Plasma Concentration (Ctrough) of M7824

Ctrough is the plasma concentration of a drug prior to administration.

Time frame:
0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Reported as:
Geometric mean · mcg/mL
Trough Plasma Concentration (Ctrough) of M7824
mcg/mLDose-escalation: M7824 0.3 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-expansion: All Solid Tumors 1200mgDose-expansion: NSCLC-2L 500 mg
Trough Plasma Concentration (Ctrough) of M7824NA ± NA2.92 ± 49.810.8 ± 32.644.0 ± 20.892.8 ± 33.3164 ± 31.2219 ± 33.975.0 ± 42.034.8 ± 82.9
SecondaryApparent Plasma Clearance (CL) of M7824

CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.

Time frame:
0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Reported as:
Geometric mean · milliliter per hour per kg(mL/h/kg)
Apparent Plasma Clearance (CL) of M7824
milliliter per hour per kg(mL/h/kg)Dose-escalation: M7824 0.3 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-expansion: All Solid Tumors 1200mgDose-expansion: NSCLC-2L 500 mg
Apparent Plasma Clearance (CL) of M78240.388 ± 30.10.270 ± 37.40.222 ± 35.20.235 ± 11.00.242 ± 28.70.194 ± 22.60.201 ± 14.30.219 ± 30.60.229 ± 38.9
SecondaryNumber of Participants With Positive Anti-Drug Antibody (ADA) of M7824

The detection of antibodies to M7824 was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive ADA of M7824 were reported.

Time frame:
Predose, up to Week 52
Reported as:
Count of participants · Participants
Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824
ParticipantsDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824120111315824821104577539189
SecondaryNumber of Participants With Best Overall Response (BOR) as Assessed by Investigator

BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Investigator. BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

Time frame:
From date of randomization up to Week 66
Reported as:
Count of participants · Participants
Number of Participants With Best Overall Response (BOR) as Assessed by Investigator
ParticipantsDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Complete response00001010001000000000101
Partial response100111101591414132541084
SecondaryDose Expansion: Number of Participants With TEAEs and Serious TEAEs

An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. TEAEs were defined as events with onset date or worsening during the on-treatment period. Serious Adverse Event (SAE) was 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. Any TEAE included participants with both serious and non-serious AEs.

Time frame:
From start of study drug administration up to 200 weeks
Reported as:
Count of participants · Participants
Dose Expansion: Number of Participants With TEAEs and Serious TEAEs
ParticipantsDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Participants with TEAEs3866318236303233343115383741
Participants with Serious TEAEs2840144929212119192312211722
SecondaryDose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death

Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants with treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

Time frame:
From start of study drug administration up to 200 weeks
Reported as:
Count of participants · Participants
Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death
ParticipantsDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Treatment-related TEAEs3044246115202225252212282731
Treatment-related Serious TEAEs5104112448593366
Treatment-related TEAE leading to death00010001100001
SecondaryDose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03

AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade \>= 3 and Grade \>=4 TEAEs were reported.

Time frame:
From start of study drug administration up to 200 weeks
Reported as:
Count of participants · Participants
Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03
ParticipantsDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC Biomarker
Grade >= 3 TEAE2952156231262220202414262427
Grade >= 4 TEAE111322491091161016710
Treatment-related Grade >= 3 TEAE7174196746611310137
Treatment-related Grade >= 4 TEAE01021001200123

Adverse events

Collected over From start of study drug administration up to 200 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dose-escalation: M7824 0.3 - 10 mg/kg2/3 (66.7%)2/3 (66.7%)3/3 (100%)
Dose-escalation: M7824 1 mg/kg3/3 (100%)2/3 (66.7%)3/3 (100%)
Dose-escalation: M7824 1 - 1200 mg4/4 (100%)2/4 (50%)4/4 (100%)
Dose-escalation: M7824 10 mg/kg3/6 (50%)1/6 (16.7%)6/6 (100%)
Dose-escalation: M7824 20 mg/kg8/10 (80%)8/10 (80%)10/10 (100%)
Dose-escalation: M7824 2400 mg/Infusion2/3 (66.7%)2/3 (66.7%)3/3 (100%)
Dose-escalation: M7824 3 mg/kg3/3 (100%)1/3 (33.3%)3/3 (100%)
Dose-escalation: M7824 30 mg/kg3/7 (42.9%)3/7 (42.9%)7/7 (100%)
Dose-expansion: Cervical Cancer8/15 (53.3%)12/15 (80%)15/15 (100%)
Dose-expansion: Colorectal Carcinoma23/32 (71.9%)21/32 (65.6%)32/32 (100%)
Dose-expansion: Esophageal Adenocarcinoma26/30 (86.7%)21/30 (70%)30/30 (100%)
Dose-expansion: Glioblastoma27/35 (77.1%)19/35 (54.3%)34/35 (97.1%)
Dose-expansion: HCC-2L53/68 (77.9%)40/68 (58.8%)66/68 (97.1%)
Dose-escalation: HCC-3 mg/kg6/6 (100%)1/6 (16.7%)6/6 (100%)
Dose-expansion: HCC Ascending Dose 1200mg25/38 (65.8%)28/38 (73.7%)38/38 (100%)
Dose-expansion: Melanoma PD-L1 Fail25/32 (78.1%)14/32 (43.8%)31/32 (96.9%)
Dose-expansion: NSCLC-2L 1200 mg26/40 (65%)21/40 (52.5%)38/40 (95%)
Dose-expansion: NSCLC-2L 500 mg30/40 (75%)17/40 (42.5%)37/40 (92.5%)
Dose-expansion: NSCLC Biomarker20/41 (48.8%)22/41 (53.7%)41/41 (100%)
Dose-expansion: NSCLC PD-L1 Fail73/83 (88%)49/83 (59%)82/83 (98.8%)
Dose-expansion: Pancreatic Adenocarcinoma29/36 (80.6%)29/36 (80.6%)36/36 (100%)
Dose-expansion: Squamous Cell Carcinoma of Head and Neck22/32 (68.8%)23/32 (71.9%)31/32 (96.9%)
Dose-expansion: Triple Negative Breast Cancer26/33 (78.8%)19/33 (57.6%)33/33 (100%)
Most frequent serious events
Showing 10 of 249
Most frequent serious events
EventDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: M7824 3 mg/kgDose-escalation: M7824 30 mg/kgDose-expansion: Cervical CancerDose-expansion: Colorectal CarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: GlioblastomaDose-expansion: HCC-2LDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC BiomarkerDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Triple Negative Breast Cancer
AnaemiaBlood and lymphatic system disorders0/30/30/40/63/100/31/31/71/152/321/300/353/681/61/382/320/400/402/411/833/364/322/33
Abdominal painGastrointestinal disorders0/31/31/40/62/100/30/31/70/150/320/300/350/680/61/380/320/400/400/410/833/360/320/33
DiarrhoeaGastrointestinal disorders0/31/30/40/61/100/30/30/70/150/320/301/350/680/60/380/321/400/400/410/830/360/320/33
Large intestinal obstructionGastrointestinal disorders0/30/30/40/60/101/30/30/70/150/320/300/350/680/60/380/320/400/400/410/830/360/320/33
NauseaGastrointestinal disorders0/31/30/41/61/100/30/31/70/150/321/300/350/680/62/381/320/400/400/410/831/360/320/33
VomitingGastrointestinal disorders0/31/30/41/61/100/30/31/70/151/320/301/350/680/62/380/320/400/400/410/831/360/321/33
Localised oedemaGeneral disorders0/31/30/40/61/100/30/30/70/150/320/300/350/680/60/380/320/400/400/410/830/360/320/33
Skin infectionInfections and infestations0/30/30/40/60/100/31/30/70/150/320/300/350/680/60/380/320/400/400/410/830/360/320/33
Soft tissue infectionInfections and infestations0/31/30/40/60/100/30/30/70/150/320/300/350/680/61/380/320/400/400/410/830/360/320/33
DehydrationMetabolism and nutrition disorders0/31/30/40/61/100/30/30/70/150/320/300/350/680/61/380/320/401/400/410/830/360/320/33
Most frequent other events
Showing 10 of 298
Most frequent other events
EventDose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: M7824 3 mg/kgDose-escalation: M7824 30 mg/kgDose-expansion: Cervical CancerDose-expansion: Colorectal CarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: GlioblastomaDose-expansion: HCC-2LDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC BiomarkerDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Triple Negative Breast Cancer
FatigueGeneral disorders1/33/34/42/66/102/30/34/75/1512/329/305/3516/683/619/3810/321/406/4010/4116/8312/364/323/33
AnaemiaBlood and lymphatic system disorders1/30/31/42/65/102/31/34/77/1510/3211/303/3524/681/69/386/326/409/4013/4125/8312/3611/329/33
ConstipationGastrointestinal disorders1/32/31/40/60/100/31/33/76/1512/328/305/357/684/611/383/322/406/406/4115/8310/366/326/33
DiarrhoeaGastrointestinal disorders0/31/31/40/61/102/31/32/74/158/325/305/3511/681/69/385/323/409/409/4114/836/364/328/33
NauseaGastrointestinal disorders1/32/31/41/63/100/32/31/73/1512/326/304/3515/681/612/387/324/4010/409/4111/8310/364/325/33
VomitingGastrointestinal disorders1/32/30/41/61/100/32/30/74/157/327/304/359/680/68/383/323/406/408/418/838/363/324/33
PyrexiaGeneral disorders0/32/31/41/62/101/30/31/72/157/322/301/356/680/614/383/329/407/406/4110/838/368/328/33
Blood creatinine increasedInvestigations1/32/30/40/62/100/30/31/70/151/321/300/353/680/63/380/320/400/403/414/831/361/321/33
Lymphocyte count decreasedInvestigations2/30/32/41/63/100/30/30/70/150/321/302/350/680/61/381/320/400/404/411/831/362/321/33
Decreased appetiteMetabolism and nutrition disorders0/32/31/41/64/100/30/31/73/1510/326/306/3518/680/67/387/329/4012/4012/4129/8310/366/328/33

Baseline characteristics

Full Analysis Set (FAS) included all participants who received at least 1 dose of IMP.

Age, Categorical
Age, Categorical(Participants)Dose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC BiomarkerTotal
<=18 years000000000000000000000000
Between 18 and 65 years2131694232328164623192131302213251917364
>=65 years1212013131540163713111125102152124236
Sex: Female, Male
Sex: Female, Male(Participants)Dose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC BiomarkerTotal
Female213235520611132714216331151571618217
Male12113521632571956222816024270332423383
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Dose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC BiomarkerTotal
Hispanic or Latino0200111036200201010011123
Not Hispanic or Latino3143596232649265533273123281714393938481
Unknown or Not Reported00000001061762813010615100296
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Dose-escalation: M7824 0.3 - 10 mg/kgDose-escalation: M7824 1 mg/kgDose-escalation: M7824 1 - 1200 mgDose-escalation: M7824 3 mg/kgDose-escalation: M7824 10 mg/kgDose-escalation: M7824 20 mg/kgDose-escalation: M7824 30 mg/kgDose-escalation: M7824 2400 mg/InfusionDose-escalation: HCC-3 mg/kgDose-expansion: HCC Ascending Dose 1200mgDose-expansion: HCC-2LDose-expansion: Melanoma PD-L1 FailDose-expansion: NSCLC PD-L1 FailDose-expansion: Pancreatic AdenocarcinomaDose-expansion: Esophageal AdenocarcinomaDose-expansion: Colorectal CarcinomaDose-expansion: Triple Negative Breast CancerDose-expansion: GlioblastomaDose-expansion: Squamous Cell Carcinoma of Head and NeckDose-expansion: Cervical CancerDose-expansion: NSCLC-2L 1200 mgDose-expansion: NSCLC-2L 500 mgDose-expansion: NSCLC BiomarkerTotal
American Indian or Alaska Native000001100000000000000002
Asian0100000001126011220105225153104
Native Hawaiian or Other Pacific Islander000000000000000000000000
Black or African American1000111101202702401110026
White2242575161322264025252918271210142530350
More than one race0001010107202200323100025
Unknown or Not Reported0000000006166280317611100893
08

Study locations

118 sites
  • Arizona Clinical Research Center
    Tucson, Arizona 85715, United States
  • Pacific Oncology Associates
    Escondido, California 92025, United States
  • University of California Davis Health System
    Sacramento, California 95817, United States
  • California Pacific Medical Center
    San Francisco, California 94118, United States
  • Innovative Clinical Research Institute
    Whittier, California 90603, United States
  • Rocky Mountain Cancer Centers, LLP
    Denver, Colorado 80218, United States
  • Eastern Connecticut Hematology/Oncology Assoc.
    Norwich, Connecticut 06360, United States
  • Sylvester Cancer Center
    Miami, Florida 33136, United States
  • Hematology - Oncology Associates of Treasure Coast
    Port Saint Lucie, Florida 34952, United States
  • University Cancer & Blood Center, LLC
    Athens, Georgia 30607, United States
  • Southeastern Regional Medical Center
    Newnan, Georgia 30265, United States
  • Metairie Oncologists, LLC
    Metairie, Louisiana 70006, United States
  • National Cancer Institute
    Bethesda, Maryland 20892, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Henry Ford Health System
    Detroit, Michigan 48202, United States
  • Michigan State University
    Lansing, Michigan 48910, United States
  • Washington University
    St Louis, Missouri 63110, United States
  • Comprehensive Cancer Centers of Nevada
    Las Vegas, Nevada 89169, United States
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27599, United States
  • UC Health Clinical Trials Office
    Cincinnati, Ohio 45206, United States
  • Case Comprehensive Cancer Center
    Cleveland, Ohio 44106, United States
  • Penn State University Milton S. Hershey Medical Center
    Hershey, Pennsylvania 17033, United States
  • Rhode Island Hospital
    Providence, Rhode Island 02903, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Greenville Hospital System University Medical Center (ITOR)
    Greenville, South Carolina 29605, United States
  • Tennessee Cancer Specialists
    Knoxville, Tennessee 37909, United States
  • Texas Oncology, P.A. - Austin
    Austin, Texas 78705, United States
  • Mary Crowley Cancer Research Centers
    Dallas, Texas 75230, United States
  • Texas Oncology, P.A. - Fort Worth
    Fort Worth, Texas 76104, United States
  • Oncology Consultants, P.A.
    Houston, Texas 77030, United States
  • University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics
    Houston, Texas 77030, United States
  • South Texas Accelerated Research Therapeutics, LLC
    San Antonio, Texas 78229, United States
  • Texas Oncology, P.A. - Tyler
    Tyler, Texas 75702, United States
  • Virginia Cancer Specialists, PC
    Fairfax, Virginia 22031, United States
  • Virginia Oncology Associates - Hampton
    Norfolk, Virginia 23502, United States
  • Compass Oncology
    Vancouver, Washington 98684, United States
  • Blacktown Hospital
    Blacktown, New South Wales 2148, Australia
  • St George Hospital
    Kogarah, New South Wales 2217, Australia
  • Liverpool Hospital
    Liverpool, New South Wales 2170, Australia
  • Port Macquarie Base Hospital
    Port Macquarie, New South Wales 2444, Australia
  • Royal North Shore Hospital
    St Leonards, New South Wales 2065, Australia
  • Calvary Mater Newcastle
    Waratah, New South Wales 2298, Australia
  • Gallipoli Medical Research Foundation Ltd
    Greenslopes, Queensland 4120, Australia
  • Tasman Oncology Research Ltd
    Southport, Queensland 4216, Australia
  • The Queen Elizabeth Hospital
    Woodville South, South Australia 5011, Australia
  • Peter MacCallum Cancer Centre-East Melbourne
    East Melbourne, Victoria 3002, Australia
  • Cabrini Hospital Malvern
    Malvern, Victoria 3144, Australia
  • Border Medical Oncology Research Unit
    Wodonga, Victoria 3690, Australia
  • Fiona Stanley Hospital
    Murdoch, Western Australia 6150, Australia
  • Linear Clinical Research Limited
    Nedlands, Western Australia 6009, Australia
  • Institut Jules Bordet
    Brussels, 1000, Belgium
  • Cliniques Universitaires Saint-Luc
    Brussels, 1200, Belgium
  • Grand Hôpital de Charleroi
    Charleroi, 6000, Belgium
  • UZ Antwerpen
    Edegem, 2650, Belgium
  • Universitair Ziekenhuis Gent
    Ghent, 9000, Belgium
  • Centre Hospitalier de l'Ardenne
    Libramont, 6800, Belgium
  • C. H. U. Sart Tilman
    Liège, 4000, Belgium
  • GZA Ziekenhuizen - Campus Sint-Augustinus
    Wilrijk, 2610, Belgium
  • Cross Cancer Institute
    Edmonton, Alberta T6G 1Z2, Canada
  • Centre Antoine Lacassagne
    Nice, Alpes Maritimes 06189, France
  • Centre Paul Strauss
    Strasbourg, Bas Rhin 67000, France
  • Hôpital de la Timone#
    Marseille, Bouches-du-Rhône 13385, France
  • Centre Georges François Leclerc
    Dijon, Côte-d'Or 21079, France
  • CHU Bordeaux - Hôpital Saint André
    Bordeaux, Gironde 33075, France
  • Institut Claudius Regaud-Oncopole
    Toulouse, Haute Garonne 31059, France
  • CHU de Grenoble - Hôpital Nord
    Grenoble, Isere 38043, France
  • ICO - Site René Gauducheau
    Saint-Herblain, Loire Atlantique 44805, France
  • Centre Oscar Lambret
    Lille, Nord 59020, France
  • Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris
    Paris, Paris 75248, France
  • Hôpital Saint-Louis
    Paris, Paris 75475, France
  • Groupe Hospitalier Pitie-Salpetriere
    Paris, Paris 75571, France
  • Centre Léon Bérard
    Lyon, Rhone 69008, France
  • Centre Hospitalier de la Croix Rousse
    Lyon, Rhone 69317, France
  • Hôpital Henri Mondor
    Créteil, Val De Marne 94010, France
  • Institut Régional du Cancer de Montpellier
    Montpellier, 34298, France
  • Medizinische Hochschule Hannover
    Hanover, Lower Saxony 30625, Germany
  • Cellex Koeln
    Cologne, North Rhine-Westphalia 50670, Germany
  • Universitaetsklinikum Carl Gustav Carus TU Dresden
    Dresden, Saxony 01307, Germany
  • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
    Berlin, 10117, Germany
  • Fondazione del Piemonte per l'Oncologia IRCC Candiolo
    Candiolo, Torino 10060, Italy
  • Ospedale San Raffaele
    Milan, 20132, Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori
    Milan, 20133, Italy
  • IEO Istituto Europeo di Oncologia
    Milan, 20141, Italy
  • Istituto Nazionale Tumori Fondazione G. Pascale
    Naples, 80131, Italy
  • Fondazione IRCCS Policlinico San Matteo
    Pavia, 27100, Italy
  • Azienda Ospedaliero Universitaria Pisana
    Pisa, 56126, Italy
  • Policlinico Universitario Agostino Gemelli
    Roma, 00168, Italy
  • A.O.U. Senese Policlinico Santa Maria alle Scotte
    Siena, 53100, Italy
  • National Cancer Center Hospital East
    Kashiwa-shi, Chiba 277-8577, Japan
  • Kindai University Hospital
    Osakasayama-shi, Osaka 589-8511, Japan
  • Seoul National University Bundang Hospital
    Seongnam-si, Gyeonggi-do 13620, South Korea
  • Chungbuk National University Hospital
    Cheongju-si, North Chungcheong 28644, South Korea
  • Pusan National University Hospital
    Busan, 49241, South Korea
  • Seoul National University Hospital
    Seoul, 03080, South Korea
  • Asan Medical Center
    Seoul, 05505, South Korea
  • Samsung Medical Center
    Seoul, 135-710, South Korea
  • Hospital Infanta Cristina
    Badajoz, 06080, Spain
  • Hospital Universitari Vall d'Hebron
    Barcelona, 08035, Spain
  • Hospital Clinic i Provincial de Barcelona
    Barcelona, 08036, Spain
  • Hospital General Universitario Gregorio Marañon
    Madrid, 28007, Spain

Showing the first 100 of 118 sites across 12 countries.

09

References and documents

Publications

  • Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C, Lamping E, Burmeister A, Marte JL, Cordes LM, Bilusic M, Karzai F, Ojalvo LS, Jehl G, Rolfe PA, Hinrichs CS, Madan RA, Schlom J, Gulley JL. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother Cancer. 2020 Dec;8(2):e001395. doi: 10.1136/jitc-2020-001395. PubMed 33323462 ↗
  • Cho BC, Daste A, Ravaud A, Salas S, Isambert N, McClay E, Awada A, Borel C, Ojalvo LS, Helwig C, Rolfe PA, Gulley JL, Penel N. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort. J Immunother Cancer. 2020 Jul;8(2):e000664. doi: 10.1136/jitc-2020-000664. PubMed 32641320 ↗
  • Wilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5. PubMed 31278692 ↗
  • Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFbeta, in Advanced Solid Tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653. Epub 2018 Jan 3. PubMed 29298798 ↗
  • Tan B, Khattak A, Felip E, Kelly K, Rich P, Wang D, Helwig C, Dussault I, Ojalvo LS, Isambert N. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-beta and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Target Oncol. 2021 Jul;16(4):435-446. doi: 10.1007/s11523-021-00809-2. Epub 2021 May 19. PubMed 34009501 ↗
  • Lim HY, Heo J, Peguero JA, Ryoo BY, Decaens T, Barlesi F, Moehler MH, Jehl G, Eggleton SP, Bajars M, Gulley JL. Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC. Hepatology. 2025 Jan 1;81(1):32-43. doi: 10.1097/HEP.0000000000001054. Epub 2024 Aug 13. PubMed 39141577 ↗
  • Rajan A, Abdul Sater H, Rahma O, Agajanian R, Lassoued W, Marte JL, Tsai YT, Donahue RN, Lamping E, Bailey S, Weisman A, Walter-Rodriguez B, Ito R, Vugmeyster Y, Sato M, Machl A, Schlom J, Gulley JL. Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with advanced non-small cell lung cancer. J Immunother Cancer. 2024 Mar 13;12(3):e008480. doi: 10.1136/jitc-2023-008480. PubMed 38485188 ↗
  • Spira A, Awada A, Isambert N, Lorente D, Penel N, Zhang Y, Ojalvo LS, Hicking C, Rolfe PA, Ihling C, Dussault I, Locke G, Borel C. Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer. Front Oncol. 2022 Dec 8;12:981940. doi: 10.3389/fonc.2022.981940. eCollection 2022. PubMed 36568239 ↗
  • Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6. PubMed 36066618 ↗

Study documents

  • Study protocol · Jun 22, 2021
  • Statistical analysis plan · Apr 5, 2022

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

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02517398
Lead sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
Responsible party
Sponsor
First posted
Aug 7, 2015
Start date
Aug 31, 2015
Primary completion
May 23, 2022
Completion
May 23, 2022
Results posted
May 3, 2024
Last update
May 3, 2024

Study contacts

Medical Responsible
study director · EMD Serono Research & Development Institute, Inc, an affiliate of MerckKGaA, Darmstadt, Germany

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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