A Study of LY3415244 in Participants With Advanced Solid Tumors

October 21, 2021 updated by: Eli Lilly and Company

A Phase 1a/1b Study of LY3415244, a Bispecific Antibody in Patients With Advanced Solid Tumors

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Administered IV
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.
Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
Time Frame: Baseline through Cycle 1 (28 Day Cycle)
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.
Baseline through Cycle 1 (28 Day Cycle)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244
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
Cmin of LY3415244 was evaluated.
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
Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
Time Frame: Baseline through Measured Progressive Disease (Up To 24 Months)
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.
Baseline through Measured Progressive Disease (Up To 24 Months)
Phase1b: Duration of Response (DoR)
Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)
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.
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)
Phase1b: Time to Response (TTR)
Time Frame: Baseline to Date of CR or PR (Up To 24 Months)
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.
Baseline to Date of CR or PR (Up To 24 Months)
Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
Time Frame: Baseline through Measured Progressive Disease (Up To 24 Months)
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.
Baseline through Measured Progressive Disease (Up To 24 Months)
Phase1b: Progression Free Survival (PFS)
Time Frame: Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)
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.
Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 22, 2018

Primary Completion (ACTUAL)

October 9, 2019

Study Completion (ACTUAL)

October 9, 2019

Study Registration Dates

First Submitted

November 16, 2018

First Submitted That Met QC Criteria

November 21, 2018

First Posted (ACTUAL)

November 23, 2018

Study Record Updates

Last Update Posted (ACTUAL)

October 22, 2021

Last Update Submitted That Met QC Criteria

October 21, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17099
  • J1C-MC-JZDA (OTHER: Eli Lilly and Company)
  • 2018-001598-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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