A Study of LY3415244 in Participants With Advanced Solid Tumors

Phase 1TerminatedNCT03752177

Eli Lilly and Company12 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor

Interventions

LY3415244DRUG

Administered IV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (6)

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Institut Jules Bordet

Brussels, Belgium

Universitair Ziekenhuis Gent

Ghent, Belgium

Outcomes

Primary Outcomes

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

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

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.

Data from ClinicalTrials.gov

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