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

• ClinicalTrials.gov Identifier: NCT02443324
• Recruitment Status: Completed
• First Posted: May 13, 2015
• Last Update Posted: August 18, 2022
• Sponsor: Eli Lilly and Company
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 11, 2015
• First Posted Date: May 13, 2015
• Last Update Posted Date: August 18, 2022
• Actual Study Start Date: July 29, 2015
• Actual Primary Completion Date: August 31, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 11, 2015): Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [ Time Frame: Baseline to Measured Progressive Disease (Estimated up to 24 Months) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 11, 2015)

• 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) ]
• 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) ]
• 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) ]
• Time to First Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Estimated up 24 Months) ]
• Progression Free Survival (PFS) [ Time Frame: Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months) ]
• Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Estimated up 24 Months) ]
• Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab [ Time Frame: Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Ramucirumab
  Administered IV
  Other Names:

  • LY3009806
  • IMC-1121B
  • Cyramza
• Drug: Pembrolizumab
  Administered IV
  Other Name: MK3475

Study Arms

• Experimental: Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)
  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.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1a Schedule 2)
  Gastric, NSCLC, Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort A)
  Gastric-GEJ: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort A1)
  BTC: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort A2)
  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.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort B)
  Gastric-GEJ: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort C)
  NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort D)
  Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab
• Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort E)
  NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
  Interventions:

  • Drug: Ramucirumab
  • Drug: Pembrolizumab

Publications *

• Herbst RS, Arkenau HT, Bendell J, Arrowsmith E, Wermke M, Soriano A, Penel N, Santana-Davila R, Bischoff H, Chau I, Mi G, Wang H, Rasmussen E, Ferry D, Chao BH, Paz-Ares L. Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. J Thorac Oncol. 2021 Feb;16(2):289-298. doi: 10.1016/j.jtho.2020.10.004. Epub 2020 Oct 15.
• Herbst RS, Arkenau HT, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, Isambert N, Soriano A, Wermke M, Cultrera J, Gao L, Widau RC, Mi G, Jin J, Ferry D, Fuchs CS, Petrylak DP, Chau I. Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. Lancet Oncol. 2019 Aug;20(8):1109-1123. doi: 10.1016/S1470-2045(19)30458-9. Epub 2019 Jul 10.
• Arkenau HT, Martin-Liberal J, Calvo E, Penel N, Krebs MG, Herbst RS, Walgren RA, Widau RC, Mi G, Jin J, Ferry D, Chau I. Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open-Label, Phase I Trial (JVDF). Oncologist. 2018 Dec;23(12):1407-e136. doi: 10.1634/theoncologist.2018-0044. Epub 2018 May 31.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 9, 2022): 298
• Original Estimated Enrollment (submitted: May 11, 2015): 92
• Actual Study Completion Date: April 12, 2022
• Actual Primary Completion Date: August 31, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Japan, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT02443324
• Other Study ID Numbers: 15787; I4T-MC-JVDF ( Other Identifier: Eli Lilly and Company ); 2015-001473-40 ( EudraCT Number ); KEYNOTE -098 ( Other Identifier: Merck )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: August 2022