A Study of LY3200882 and Pembrolizumab 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 see if the drug LY3200882 which is an inhibitor of transforming growth factor-β (TGFβ) receptor 1 in combination with pembrolizumab is safe and effective in participants with cancer that has spread to other parts of the body.

Official Title
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Phase 1b/2 Study of LY3200882 and Pembrolizumab in Patients With Advanced Cancer

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: LY3200882
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have received a PD-1 PDLI therapy within 9 weeks of starting dosing on this study [for example, nivolumab, pembrolizumab, atezolizumab] Participants must be willing to have tumor biopsies Participants must have adequate organ function Participants must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Participants must be able to swallow tablets Participants with stable, previously treated brain metastases may participate if neurologic symptoms have resolved and participants have been off steroids for at least 14 days Exclusion Criteria: Participants must not have moderate or severe cardiovascular disease Participants must not have active autoimmune disease (for example Crohn's disease, Hashimotos disease, etc) Participants must not have an active infection requiring treatment

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3200882 and Pembrolizumab (Dose Level 1)<br>Participants with urothelial carcinoma: LY3200882 administered orally with pembrolizumab administered intravenously (IV). | Drug: LY3200882<br>* LY3200882 administered orally<br>Drug: Pembrolizumab<br>* Pembrolizumab administered IV<br>|
| Experimental: LY3200882 and Pembrolizumab (Dose Level 2)<br>Participants with urothelial carcinoma: LY3200882 administered orally with pembrolizumab administered IV. | Drug: LY3200882<br>* LY3200882 administered orally<br>Drug: Pembrolizumab<br>* Pembrolizumab administered IV<br>|
| Experimental: LY3200882 and Pembrolizumab Expansion<br>Participants with urothelial carcinoma, non-small cell lung cancer, or hepatocellular carcinoma: LY3200882 administered orally twice in combination with pembrolizumab administered IV. | Drug: LY3200882<br>* LY3200882 administered orally<br>Drug: Pembrolizumab<br>* Pembrolizumab administered IV<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 Toxicity (DLT) | Number of Participants with DLT | Up to 6 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) | ORR: Percentage of Participants with CR or PR | Baseline through Disease Progression or Death (Estimated at up to 12 Months) | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3200882 in Combination With Pembrolizumab | PK: Cmax of LY3200882 in Combination With Pembrolizumab | Baseline through Week 13 | 
| Duration of Response (DoR) | DoR | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 12 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TGF-beta, Urothelial carcinoma, Hepatocellular carcinoma, Non-small cell lung cancer, TGF- beta receptor type I inhibitor