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TerminatedNCT03752177Updated Oct 22, 2021Results posted

A Study of LY3415244 in Participants With Advanced Solid Tumors

A Phase 1 interventional study of LY3415244 in Solid Tumor, sponsored by Eli Lilly and Company. Terminated at 6 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-22.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Treatment

Why this study was terminated
The study was terminated during dose escalation after a determination was made that the risk:benefit ratio no longer favored continued evaluation.
Phase
Phase 1
Study type
Interventional
Enrollment
12
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The goal of this study is to evaluate the safety of LY3415244, a PD-L1/TIM-3 bispecific antibody, administered as monotherapy to participants with advanced solid tumors.

02

Conditions studied

  • Solid Tumor

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Keywords

  • TIM-3
  • PD-L1
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 12 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) 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

  • For Phase 1a/b, histologic or cytologic confirmation of advanced solid tumor.
  • For Phase 1a/b, biopsy of tumor samples are required. Newly obtained core or excisional biopsy of a tumor lesion prior to study enrollment and undergo a biopsy procedure during the study.
  • Phase 1a, prior anti-PD-1 or anti-PD-L1 therapy or other immunotherapy is allowed.

  • Phase 1b, prior anti-PD-1 or anti-PD-L1 therapy is required where anti-PD-1 or anti-PD-L1 is standard of care in respective tumor types if the following criteria are met:

    • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
    • Must have completely recovered to baseline level prior to screening from any adverse events (AEs) that occurred from receiving prior immunotherapy
    • Must not have experienced a Grade ≥3 immune-related AE or immune related neurologic or ocular AE, pneumonitis or cardiomyopathy of any grade while receiving prior immunotherapy
    • Must not have required immunosuppressive agent, other than corticosteroids for the management of an adverse event and not currently require maintenance doses of >10 milligrams (mg) prednisone (or equivalent) per day
  • Must have at least 1 measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Have adequate organ function.
  • Have an estimated life expectancy ≥12 weeks, in the judgement of the investigator.

Exclusion criteria

Exclusion Criteria:

  • Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days.
  • Have received a live vaccine within 30 days before the first dose of study treatment.
  • If female, is pregnant, breastfeeding, or planning to become pregnant.
  • Have a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's participation.
  • Have moderate or severe cardiovascular disease.
  • Have a serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment.
  • Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, cyclosporine). [Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted].
  • Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
  • Evidence of interstitial lung disease or noninfectious pneumonitis.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
12 participants (actual)

Study arms

  • Experimental
    LY3415244 Dose Escalation

    Participants received 3 milligrams (mg) LY3415244 (Cohort A1), 10 mg LY3415244 (Cohort A2), 30 mg LY3415244 (Cohort A3) and 70 mg LY3415244 (Cohort A4) as an intravenous (IV) infusion on day (D)1 and D15 of each 28-day cycle every 2 weeks (Q2W).

    Drug: LY3415244

  • Experimental
    LY3415244 Dose Expansion

    Phase 1b dose expansion was planned but not initiated as dose escalation ended at cohort A4. Study did not achieve its primary objective of establishing a recommended phase 2 dose (RP2D) due to early termination of the study by Cohort A4.

    Drug: LY3415244

Interventions

  • DrugLY3415244

    Administered IV

06

What researchers measure

Primary outcomes

  1. Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)

    A DLT was defined as an adverse event (AE) occurring during Cycle 1(28 days) that was considered at least possibly related to study drug, was considered dose-dependent, and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 \[NCI-CTCAE v 4.0\] \[NCI 2009\]):Grade 3 thrombocytopenia requiring platelet transfusion or grade 4 thrombocytopenia. Grade greater than or equal to (≥) 3 febrile neutropenia, anemia requiring a blood transfusion and any other Grade 4 hematologic toxicity that last \>7 days. Grade ≥ 3 colitis or noninfectious pneumonitis, Grade ≥ 3 fatigue lasting \>7 days, Grade ≥ 3 hypertension despite of maximal medical therapy. Grade 4 immune-related adverse event (irAE), liver transaminase elevation \>8x upper limit of normal (ULN) or total bilirubin \>3x ULN.

    Time frame: Baseline through Cycle 1 (28 Day Cycle)

Secondary outcomes

  1. Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244

    Cmin of LY3415244 was evaluated.

    Time frame: Cycle 1 Day 1 (C1D1) and C1D15: pre-dose, 2 hours(h), 4h, 24h, 72h, 120h and 168h post-dose; C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1 and C6D15: pre-dose

  2. Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)

    ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

    Time frame: Baseline through Measured Progressive Disease (Up To 24 Months)

  3. Phase1b: Duration of Response (DoR)

    Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to \<10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.

    Time frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)

  4. Phase1b: Time to Response (TTR)

    Data were not captured as study was terminated early and no participant were enrolled into Phase 1b expansion. Time to treatment response was defined as date of first dose of study drug to the date of confirmed complete response (CR) or partial response (PR) using Response evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    Time frame: Baseline to Date of CR or PR (Up To 24 Months)

  5. Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease

    DCR is the percentage of participants with a best overall response of CR, PR or stable disease (SD) as defined by RECIST v1.1. CR is defined as disappearance of all target and non-target lesions and no appearance of new lesions.PR is defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions (taking as reference the baseline sum LD),no progression of non-target lesions, and no appearance of new lesions.SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.

    Time frame: Baseline through Measured Progressive Disease (Up To 24 Months)

  6. Phase1b: Progression Free Survival (PFS)

    Progression-free survival time was measured from treatment start until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Patients who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of treatment start if no post-baseline radiographic assessment is available.

    Time frame: Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)

07

Results

Posted Aug 31, 2021
Limitations and caveats
Phase 1b dose expansion was planned but not initiated as dose escalation ended at cohort A4. Study did not achieve its primary objective of establishing a recommended phase 2 dose (RP2D) due to early termination of the study.

Participant flow

Participant flow — Overall Study
MilestoneCohort A1Cohort A2Cohort A3Cohort A4
Started3333
Received at least 1 dose of study drug3333
Completed3333
Not completed0000

Outcome measures

PrimaryPhase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)

A DLT was defined as an adverse event (AE) occurring during Cycle 1(28 days) that was considered at least possibly related to study drug, was considered dose-dependent, and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 \[NCI-CTCAE v 4.0\] \[NCI 2009\]):Grade 3 thrombocytopenia requiring platelet transfusion or grade 4 thrombocytopenia. Grade greater than or equal to (≥) 3 febrile neutropenia, anemia requiring a blood transfusion and any other Grade 4 hematologic toxicity that last \>7 days. Grade ≥ 3 colitis or noninfectious pneumonitis, Grade ≥ 3 fatigue lasting \>7 days, Grade ≥ 3 hypertension despite of maximal medical therapy. Grade 4 immune-related adverse event (irAE), liver transaminase elevation \>8x upper limit of normal (ULN) or total bilirubin \>3x ULN.

Time frame:
Baseline through Cycle 1 (28 Day Cycle)
Reported as:
Count of participants · Participants
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
ParticipantsCohort A1Cohort A2Cohort A3Cohort A4
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)0000
SecondaryPhase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244

Cmin of LY3415244 was evaluated.

Time frame:
Cycle 1 Day 1 (C1D1) and C1D15: pre-dose, 2 hours(h), 4h, 24h, 72h, 120h and 168h post-dose; C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1 and C6D15: pre-dose
Reported as:
Geometric mean · nanograms per milliliter (ng/mL)
Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244
nanograms per milliliter (ng/mL)Cohort A1Cohort A2Cohort A3Cohort A4
Cycle 1 Day 1——NA ± NA4270 ± 26
Cycle 1 Day 15—NA ± NANA ± NA—
SecondaryPhase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Time frame:
Baseline through Measured Progressive Disease (Up To 24 Months)

No measurements were reported for this outcome.

SecondaryPhase1b: Duration of Response (DoR)

Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to \<10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.

Time frame:
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)

No measurements were reported for this outcome.

SecondaryPhase1b: Time to Response (TTR)

Data were not captured as study was terminated early and no participant were enrolled into Phase 1b expansion. Time to treatment response was defined as date of first dose of study drug to the date of confirmed complete response (CR) or partial response (PR) using Response evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Time frame:
Baseline to Date of CR or PR (Up To 24 Months)

No measurements were reported for this outcome.

SecondaryPhase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease

DCR is the percentage of participants with a best overall response of CR, PR or stable disease (SD) as defined by RECIST v1.1. CR is defined as disappearance of all target and non-target lesions and no appearance of new lesions.PR is defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions (taking as reference the baseline sum LD),no progression of non-target lesions, and no appearance of new lesions.SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.

Time frame:
Baseline through Measured Progressive Disease (Up To 24 Months)

No measurements were reported for this outcome.

SecondaryPhase1b: Progression Free Survival (PFS)

Progression-free survival time was measured from treatment start until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Patients who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of treatment start if no post-baseline radiographic assessment is available.

Time frame:
Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)

No measurements were reported for this outcome.

Adverse events

Collected over Up To 24 Months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort A12/3 (66.7%)0/3 (0%)3/3 (100%)
Cohort A20/3 (0%)0/3 (0%)3/3 (100%)
Cohort A30/3 (0%)0/3 (0%)3/3 (100%)
Cohort A40/3 (0%)2/3 (66.7%)3/3 (100%)
Most frequent serious events
Most frequent serious events
EventCohort A1Cohort A2Cohort A3Cohort A4
Gastrointestinal stoma complicationInjury, poisoning and procedural complications0/30/30/31/3
Infusion related reactionInjury, poisoning and procedural complications0/30/30/31/3
Most frequent other events
Showing 10 of 69
Most frequent other events
EventCohort A1Cohort A2Cohort A3Cohort A4
FatigueGeneral disorders0/31/33/31/3
ConstipationGastrointestinal disorders0/31/32/30/3
Oedema peripheralGeneral disorders0/32/30/30/3
CoughRespiratory, thoracic and mediastinal disorders1/30/32/30/3
DyspnoeaRespiratory, thoracic and mediastinal disorders1/31/32/30/3
AnaemiaBlood and lymphatic system disorders0/30/31/30/3
VertigoEar and labyrinth disorders0/30/30/31/3
Eye movement disorderEye disorders1/30/30/30/3
Eye painEye disorders0/30/31/30/3
Eyelid ptosisEye disorders1/30/30/30/3

Baseline characteristics

All enrolled participants.

Age, Continuous
Age, Continuous(years)Cohort A1Cohort A2Cohort A3Cohort A4Total
Mean53.33 ± 2.3157.00 ± 11.3648.33 ± 20.6055.67 ± 3.7953.58 ± 10.77
Sex: Female, Male
Sex: Female, Male(Participants)Cohort A1Cohort A2Cohort A3Cohort A4Total
Female22116
Male11226
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort A1Cohort A2Cohort A3Cohort A4Total
Hispanic or Latino00000
Not Hispanic or Latino22318
Unknown or Not Reported11024
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort A1Cohort A2Cohort A3Cohort A4Total
American Indian or Alaska Native00000
Asian21014
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White12328
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(Participants)Cohort A1Cohort A2Cohort A3Cohort A4Total
Belgium01225
United States11103
Japan21014
08

Study locations

6 sites
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
  • Institut Jules Bordet
    Brussel, 1000, Belgium
  • Universitair Ziekenhuis Gent
    Gent, 9000, Belgium
  • National Cancer Center Hospital East
    Kashiwa, Chiba 277 8577, Japan
  • National Cancer Center Hospital
    Chuo-Ku, Tokyo 104-0045, Japan
09

References and documents

Study documents

  • Study protocol · Dec 13, 2018
  • Statistical analysis plan · Oct 24, 2018

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

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 22, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03752177
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Nov 23, 2018
Start date
Nov 22, 2018
Primary completion
Oct 9, 2019
Completion
Oct 9, 2019
Results posted
Aug 31, 2021
Last update
Oct 22, 2021

Study contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
study director · Eli Lilly and Company

Oversight

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

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