A Study of Ramucirumab Plus Pembrolizumab in Participants With Gastric or GEJ Adenocarcinoma, NSCLC, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and preliminary efficacy of the combination of the study drug known as ramucirumab plus pembrolizumab in participants with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), transitional cell carcinoma of the urothelium, or biliary tract cancer (BTC).

Official Title
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An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus Pembrolizumab in Patients With Locally Advanced and Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract Cancer

Conditions
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Gastric Adenocarcinoma, Adenocarcinoma of the Gastroesophageal Junction, Non-small Cell Lung Cancer, Carcinoma, Transitional Cell, Biliary Tract Cancer

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic disease or locally advanced, unresectable disease. Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 0-2 prior lines of systemic therapy Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 0-3 prior lines of systemic therapy Has histopathologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with documented disease progression after 1-3 prior lines of systemic therapy Has histologically confirmed biliary tract adenocarcinoma with documented progression after 1-2 prior lines of systemic therapy Availability of tumor tissue for biomarker analysis from a newly obtained core or excisional biopsy or willing to undergo a tumor biopsy. For first line NSCLC participants only, PD-L1 expression should be 1% or higher. Have an Eastern Cooperative Oncology Group Performance Status of 0 or 1. Has adequate organ function. Have an anticipated life expectancy of ≥3 months. Exclusion Criteria: Have known brain metastases. Has received ≥3 lines of prior systemic therapy for gastric or GEJ adenocarcinoma and BTC or ≥4 lines for NSCLC or urothelial cancer. Has active autoimmune disease. Known human immunodeficiency virus (HIV) infection. Known active hepatitis B or hepatitis C infection. Has received any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or VEGF receptor, or programmed death (PD) 1 or PD-ligand 1/2 signaling pathways. Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted. Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment. Have an elective or a planned major surgery during the course of the trial or has undergone major surgery within 28 days prior to enrollment.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)<br>Gastric-GEJ, BTC: Ramucirumab given intravenously (IV) on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1a Schedule 2)<br>Gastric, NSCLC, Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort A)<br>Gastric-GEJ: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort A1)<br>BTC: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort A2)<br>Gastric-GEJ (first line only): Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort B)<br>Gastric-GEJ: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort C)<br>NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort D)<br>Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort E)<br>NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) |  | Baseline to Measured Progressive Disease (Estimated up to 24 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] |  | Baseline to Measured Progressive Disease (Estimated up 24 Months) | 
| Proportion of Participants who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)] |  | Baseline to Measured Progressive Disease (Estimated up 24 Months) | 
| Duration of Response (DoR) |  | Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up 24 Months) | 
| Time to First Response (TTR) |  | Baseline to Date of CR or PR (Estimated up 24 Months) | 
| Progression Free Survival (PFS) |  | Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months) | 
| Overall Survival (OS) |  | Baseline to Death from Any Cause (Estimated up 24 Months) | 
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab |  | Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immuno-oncology, PD-1, Vascular Endothelial Growth Factor (VEGF), angiogenesis, carcinoma of the bladder, carcinoma of the urethra, carcinoma of the ureter, carcinoma of the renal pelvis, carcinoma of the biliary tract