A Study of LY3405105 in Participants With Advanced Cancer

Lilly

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor

Treatments: Drug: LY3405105

Study type: Interventional

Funder types: Industry

Identifiers

NCT03770494

2018-002668-23 (EudraCT Number)

J1F-MC-JZFA (Other Identifier)

17125

Details and patient eligibility

About

The main purpose of this study is to investigate the safety of LY3405105 in participants with advanced cancer. The study has two parts phase 1a and phase 1b. Participants will only enroll in one part.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Phase 1 a:

• Have histological or cytological evidence of a diagnosis of a solid tumor cancer that is advanced and/or metastatic
• Have available archived tissue for exploratory biomarker analysis
• Have adequate organ function
• Have discontinued all previous treatments for cancer and recovered from their side effects
• Are able to swallow capsules/tablets

Phase 1 b:

• Cohort 1: Triple-negative breast cancer (TNBC).
• Cohort 2: Clear cell ovarian cancer, endometrioid ovarian cancer, or endometrioid endometrial carcinoma with a LOF mutation in one or more of the following genes: ARID1A, KMT2C (MLL3), KMT2D (MLL2), or KDM6A (UTX).
• Cohort 3: Soft tissue sarcoma or sarcomatoid/rhabdoid malignancy with loss of expression of INI1, BRG1, or BRM by immunohistochemistry or a LOF mutation in one or more of the following genes: ARID1A, SMARCA2, SMARCA4, or SMARCB1. Participants aged ≥ 12 years with a body weight of ≥ 40 kilogram (kg) are acceptable for Cohorts 3. Participants with synovial sarcoma and a confirmed SS18-SSX gene fusion are also eligible.
• Cohort 4: Epithelioid sarcoma with INI1 loss of expression by immunohistochemistry or SMARCB1 LOF mutation. Participants aged ≥ 12 years with a body weight of ≥ 40 kilogram (kg) are acceptable for Cohorts 4.
• Cohort 5: Bladder cancer with a LOF mutation in one or more of the following genes: ARID1A, KMT2C (MLL3), KMT2D (MLL2), or KDM6A (UTX).

Exclusion criteria

• Have symptomatic central nervous system (CNS) malignancy or metastasis
• Have symptomatic human immunodeficiency virus (HIV), Hepatitis A, B, or C
• Have congestive heart failure
• Are breastfeeding

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

LY3405105

Experimental group

Description:

This study was designed to be conducted in two phases: Phase 1a: This is a dose-escalation phase with a starting dose of LY3405105 1 milligram (mg) once daily (Part A1) or 2 mg three times per week (Part A2) on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Each dose-level will be determined and will have participants enrolled to it based on dose-limiting toxicity rate observed at previous dose-level. Intermediate, alternate, or higher dose levels will be explored if deemed necessary. Phase 1b: This is a dose-expansion phase designed to explore the anti-tumor activity of recommended LY3405105 dose and dosing schedule determined in phase 1a, in participants with multiple tumor types. \[Phase 1b was planned but not initiated based on the sponsor's decision and limited efficacy observed in phase 1a\]

Treatment:

Drug: LY3405105