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

Phase 1

Terminated

• Conditions: Solid Tumor; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Triple Negative Breast Cancer
• Interventions: Drug: LY3381916; Drug: LY3300054

• Registration Number: NCT03343613
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-09
• Study First Submitted QC: 2017-11-10
• Study Start: 2017-11-17
• Study First Posted: 2017-11-17
• Primary Completion: 2020-02-07
• Study Completion: 2020-05-04
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-08
• Last Update Posted: 2020-06-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 60

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LY3381916 Escalation	LY3381916	LY3381916 administered orally.
LY3381916 + LY3300054 Escalation	LY3381916	LY3381916 administered orally and LY3300054 administered intravenously (IV).
LY3381916 + LY3300054 Escalation	LY3300054	LY3381916 administered orally and LY3300054 administered intravenously (IV).
LY3381916 Expansion	LY3381916	LY3381916 administered orally.
LY3381916 + LY3300054 Expansion B1	LY3381916	Metastatic triple negative breast cancer (TNBC) LY3381916 administered orally and LY3300054 administered IV.
LY3381916 + LY3300054 Expansion B1	LY3300054	Metastatic triple negative breast cancer (TNBC) LY3381916 administered orally and LY3300054 administered IV.
LY3381916 + LY3300054 Expansion B2	LY3381916	Metastatic non-small cell lung cancer (NSCLC) LY3381916 administered orally and LY3300054 administered IV.
LY3381916 + LY3300054 Expansion B2	LY3300054	Metastatic non-small cell lung cancer (NSCLC) LY3381916 administered orally and LY3300054 administered IV.
LY3381916 + LY3300054 Expansion B3	LY3381916	Metastatic clear cell carcinoma renal cell carcinoma (RCC) LY3381916 administered orally and LY3300054 administered IV.
LY3381916 + LY3300054 Expansion B3	LY3300054	Metastatic clear cell carcinoma renal cell carcinoma (RCC) LY3381916 administered orally and LY3300054 administered IV.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Dose Limiting Toxicities (DLTs)	Baseline through Cycle 1 (28 Day Cycle)	Number of participants with DLTs

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY3381916	Predose Lead in Day 1 through Cycle 3 Day 1	PK: Cmax of LY3381916
PK: Area Under the Plasma Concentration Curve (AUC) of LY3381916	Predose Lead in Day 1 through Cycle 3 Day 1	PK: AUC of LY3381916
PK: Cmax of LY3381916 Administered in Combination with LY3300054	Predose Cycle 1 Day 1 through Cycle 3 Day 1	PK: Cmax 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: AUC of LY3381916 administered in combination with LY3300054
PK: Cmax of LY3300054 Administered in Combination with LY3381916	Predose Cycle 1 Day 1 through Cycle 3 Day 1	PK: Cmax of LY3300054 administered in combination with LY3381916
PK: Minimum Plasma Concentration (Cmin) of LY3300054 Administered in Combination with LY3381916	Predose Cycle 1 Day 1 through Cycle 3 Day 1	PK: Cmin of LY3300054 administered in combination with LY3381916
Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)	Baseline through Measured Progressive Disease (Estimated up to 12 Months)	ORR: Percentage of participants with a CR or PR
Time to Response (TTR)	Baseline to Date of CR or PR (Estimated up to 12 Months)	TTR
Progression Free Survival (PFS)	Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 12 Months)	PFS
Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR	Baseline through Measured Progressive Disease (Estimated up to 12 Months)	DCR: Percentage of participants who exhibit SD, CR or PR
Duration of Response (DOR)	Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)	DOR

Trial Locations

Locations (12)

IU Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Tennessee Oncology PLLC; 🇺🇸 Nashville, Tennessee, United States

Gustave Roussy; 🇫🇷 Villejuif Cedex, France

Finsen Institute; 🇩🇰 Copenhagen, Denmark

Azienda Ospedaliera Umberto I; 🇮🇹 Ancona, Italy

Universitair Ziekenhuis Antwerpen; 🇧🇪 Edegem, Belgium

Sarah Cannon Research Institute SCRI; 🇺🇸 Nashville, Tennessee, United States

Institut Jules Bordet; 🇧🇪 Brussel, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Azienda Ospedaliera San Gerardo; 🇮🇹 Monza, Milano, Italy

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinico Universitario Virgen de la Victoria; 🇪🇸 Malaga, Andalucia, Spain