A Study of LY3415244 in Participants With Advanced Solid Tumors

NCT03752177 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 17099J1C-MC-JZDA2018-001598-25
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 6

Brief 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.

Conditions

Solid Tumor

Keywords

TIM-3; PD-L1

Outcome Measures

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.

  Baseline through Cycle 1 (28 Day Cycle)

Secondary Outcomes (6)

• Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244

  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)

  Baseline through Measured Progressive Disease (Up To 24 Months)

• Phase1b: Duration of Response (DoR)

  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)

  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

  Baseline through Measured Progressive Disease (Up To 24 Months)

Study Arms (2)

LY3415244 Dose Escalation

EXPERIMENTAL

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

LY3415244 Dose Expansion

EXPERIMENTAL

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

LY3415244 DRUG

Administered IV

LY3415244 Dose Escalation; LY3415244 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (6)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277 8577, Japan

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

Related Links

• A Study of LY3415244 in Participants With Advanced Solid Tumors

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.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 23, 2018
• Study Start: November 22, 2018
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: October 22, 2021
• Results First Posted: August 31, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); JP (2); US (2)