A Study of LY3415244 in Participants With Advanced Solid Tumors

Lilly

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor

Treatments: Drug: LY3415244

Study type: Interventional

Funder types: Industry

Identifiers

NCT03752177

2018-001598-25 (EudraCT Number)

J1C-MC-JZDA (Other Identifier)

17099

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

LY3415244 Dose Escalation

Experimental group

Description:

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).

Treatment:

Drug: LY3415244

LY3415244 Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: LY3415244