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

NCT02443324

Description:

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).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Bladder Urothelial Carcinoma
  • Gastric Adenocarcinoma
  • Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma
  • Liver and Intrahepatic Bile Duct Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Pelvis Urothelial Carcinoma
  • Ureter Urothelial Carcinoma
  • Urethral Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 15787
  • SECONDARY ID: I4T-MC-JVDF
  • SECONDARY ID: 2015-001473-40
  • SECONDARY ID: KEYNOTE -098
  • NCT ID: NCT02443324

Trial Conditions

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

Trial Interventions

DrugSynonymsArms
RamucirumabLY3009806, IMC-1121B, CyramzaRamucirumab + Pembrolizumab (Phase 1a Schedule 1)
PembrolizumabMK3475Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)

Trial Purpose

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).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)ExperimentalGastric-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.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1a Schedule 2)ExperimentalGastric, NSCLC, Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1b Cohort A)ExperimentalGastric-GEJ: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1b Cohort A1)ExperimentalBTC: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1b Cohort A2)ExperimentalGastric-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.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1b Cohort B)ExperimentalGastric-GEJ: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1b Cohort C)ExperimentalNSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab
Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort D)ExperimentalUrothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab
Ramucirumab + Pembrolizumab (Phase 1b Cohort E)ExperimentalNSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  • Ramucirumab
  • Pembrolizumab

Eligibility Criteria

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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame:Baseline to Measured Progressive Disease (Estimated up to 24 Months)
Safety Issue:No
Description:

Secondary Outcome Measures

Measure:Proportion of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Time Frame:Baseline to Measured Progressive Disease (Estimated up 24 Months)
Safety Issue:No
Description:
Measure:Proportion of Participants who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]
Time Frame:Baseline to Measured Progressive Disease (Estimated up 24 Months)
Safety Issue:No
Description:
Measure:Duration of Response (DoR)
Time Frame:Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up 24 Months)
Safety Issue:No
Description:
Measure:Time to First Response (TTR)
Time Frame:Baseline to Date of CR or PR (Estimated up 24 Months)
Safety Issue:No
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months)
Safety Issue:No
Description:
Measure:Overall Survival (OS)
Time Frame:Baseline to Death from Any Cause (Estimated up 24 Months)
Safety Issue:No
Description:
Measure:Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Time Frame:Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles)
Safety Issue:No
Description:

Trial Keywords

  • immuno-oncology
  • Vascular Endothelial Growth Factor (VEGF)
  • angiogenesis
  • PD-1
  • carcinoma of the bladder
  • carcinoma of the urethra
  • carcinoma of the ureter
  • carcinoma of the renal pelvis
  • carcinoma of the biliary tract