A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of the study drug LY3381916 administered alone or in combination with anti-programmed cell death ligand 1 (PD-L1) checkpoint antibody (LY3300054).

Official Title
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A Phase 1a/1b Study of an Anti-IDO-1 Agent (LY3381916) Administered Alone or in Combination With Anti- PD-L1 Checkpoint Antibody (LY3300054) in Solid Tumors

Conditions
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Solid Tumor, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: LY3381916
* Drug: LY3300054


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dose escalation phase: Participant must have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic. Dose expansion B1: Metastatic TNBC participants who have not received prior PD-1/L1 treatment. Dose expansion B2: Metastatic NSCLC participants who have progressed on prior PD-L1/L1 treatment. Dose expansion B3: Metastatic clear cell carcinoma RCC who have progressed on prior PD-L1/L1 treatment. Have adequate organ function. Have a performance status (PS) of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. Are able and willing to provide required, newly acquired tumor biopsies. Have discontinued previous treatments for cancer. Are able to swallow capsules. Exclusion Criteria: Currently enrolled in a clinical study. Have known symptomatic central nervous system metastases or carcinomatous meningitis. Have a serious concomitant systemic disorder. Have a symptomatic human immunodeficiency virus infection or symptomatic activated/reactivated hepatitis B or C. Have a significant cardiac condition. Have previously received an indoleamine- 2,3-dioxygenase (IDO) inhibitor. Have an active autoimmune disease or currently require immunosuppression of >10 milligrams of prednisone or equivalent per day. Have interstitial lung disease or (noninfectious) pneumonitis, participants with a history of (noninfectious) pneumonitis that required steroids to assist with management.

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: LY3381916 Escalation<br>LY3381916 administered orally. | Drug: LY3381916<br>* IDO-1 inhibitor administered orally<br>|
| Experimental: LY3381916 + LY3300054 Escalation<br>LY3381916 administered orally and LY3300054 administered intravenously (IV). | Drug: LY3381916<br>* IDO-1 inhibitor administered orally<br>Drug: LY3300054<br>* PD-L1 inhibitor administered IV<br>|
| Experimental: LY3381916 Expansion<br>LY3381916 administered orally. | Drug: LY3381916<br>* IDO-1 inhibitor administered orally<br>|
| Experimental: LY3381916 + LY3300054 Expansion B1<br>Metastatic triple negative breast cancer (TNBC) LY3381916 administered orally and LY3300054 administered IV. | Drug: LY3381916<br>* IDO-1 inhibitor administered orally<br>Drug: LY3300054<br>* PD-L1 inhibitor administered IV<br>|
| Experimental: LY3381916 + LY3300054 Expansion B2<br>Metastatic non-small cell lung cancer (NSCLC) LY3381916 administered orally and LY3300054 administered IV. | Drug: LY3381916<br>* IDO-1 inhibitor administered orally<br>Drug: LY3300054<br>* PD-L1 inhibitor administered IV<br>|
| Experimental: LY3381916 + LY3300054 Expansion B3<br>Metastatic clear cell carcinoma renal cell carcinoma (RCC) LY3381916 administered orally and LY3300054 administered IV. | Drug: LY3381916<br>* IDO-1 inhibitor administered orally<br>Drug: LY3300054<br>* PD-L1 inhibitor 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 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): Maximum Plasma Concentration (Cmax) of LY3381916 | PK: Cmax of LY3381916 | Predose Lead in Day 1 through Cycle 3 Day 1 | 
| PK: Area Under the Plasma Concentration Curve (AUC) of LY3381916 | PK: AUC of LY3381916 | Predose Lead in Day 1 through Cycle 3 Day 1 | 
| PK: Cmax of LY3381916 Administered in Combination with LY3300054 | PK: Cmax of LY3381916 administered in combination with LY3300054 | Predose Cycle 1 Day 1 through Cycle 3 Day 1 | 
| PK: AUC of LY3381916 Administered in Combination with LY3300054 | PK: AUC of LY3381916 administered in combination with LY3300054 | Predose Cycle 1 Day 1 through Cycle 3 Day 1 | 
| PK: Cmax of LY3300054 Administered in Combination with LY3381916 | PK: Cmax of LY3300054 administered in combination with LY3381916 | Predose Cycle 1 Day 1 through Cycle 3 Day 1 | 
| PK: Minimum Plasma Concentration (Cmin) of LY3300054 Administered in Combination with LY3381916 | PK: Cmin of LY3300054 administered in combination with LY3381916 | Predose Cycle 1 Day 1 through Cycle 3 Day 1 | 
| Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR) | ORR: Percentage of participants with a CR or PR | Baseline through Measured Progressive Disease (Estimated up to 12 Months) | 
| Time to Response (TTR) | TTR | Baseline to Date of CR or PR (Estimated up to 12 Months) | 
| Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR | DCR: Percentage of participants who exhibit SD, CR or PR | Baseline through Measured Progressive Disease (Estimated up to 12 Months) | 
| Duration of Response (DOR) | DOR | Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months) | 
| Progression Free Survival (PFS) | PFS | Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 12 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IDO-1 Inhibitor, IDO1 Inhibitor, IDO Inhibitor