A Study of LY3405105 in Participants With Advanced Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1a/1b Study of LY3405105 Administered to Patients With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: LY3405105


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3405105<br>LY3405105 administered orally. | Drug: LY3405105<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) | Number of participants with DLTs | Baseline through Cycle 1 (28 Day Cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of LY3405105 | PK: AUC of LY3405105 | Predose Lead in Day 1 through Predose Cycle 2 Day 1 (28 Day Cycles) | 
| Objective Response Rate (ORR): Percentage of Participants with a Confirmed Complete Response (CR) or Partial Response (PR) | ORR: Percentage of participants with a Confirmed CR or PR | Baseline through Measured Progressive Disease (Estimated up to 6 Months) | 
| Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), Confirmed CR or PR | DCR: Percentage of participants who exhibit SD, Confirmed CR or PR | Baseline through Measured Progressive Disease (Estimated up to 6 Months) | 
| Duration of Response (DOR) | DOR | Date of Confirmed CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months) | 
| Time to Response (TTR) | TTR | Baseline to Date of Confirmed CR or PR (Estimated up to 6 Months) | 
| Progression Free Survival (PFS) | PFS | Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 12 Months) | 
| Overall Survival (OS) | OS | Baseline to Date of Death from Any Cause (Estimated up to 12 Months) |