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 | Completed Phase 1 Results

• 4 other identifiers: 15787I4T-MC-JVDF2015-001473-40KEYNOTE -098
• Study Type: interventional
• Target: 175
• Locations: 6 countries
• Sites: 22

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).

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• Phase 1a: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  DLT is defined as an Adverse Event (AE) that is likely related to study medication or combination,and fulfills any one of following criteria:Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade (Gr) 3 and 4 nonlaboratory toxicity (tox),Any Gr 3 or 4 laboratory value if medical intervention is required to treat participant (pt) or abnormality persists for \>1 week;Hematologic tox:Gr 4 toxicity lasting ≥ 7 days,or Gr 3 thrombocytopenia if associated with bleeding and requires platelet transfusion,or Febrile neutropenia Gr 3 or Gr 4;GR 5 tox (death);Any toxicity that is possibly related to study treatment that requires withdrawal of pt from study during Cycle 1,A delay of \> 14 days due to persistent Grade ≥ 2 toxicities in initiating Cycle 2,with exception of Grade 2 fatigue;Any infusion or hypersensitivity reactions are NOT a DLT. A summary of other nonserious AEs and all Serious AEs,regardless of causality is located in Reported Adverse Event section.

  Cycle 1 (21 Days)

Secondary Outcomes (7)

• Phase 1a and 1b: Percentage of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

  Baseline to Measured Progressive Disease (Up to 24 Months)

• Phase 1a and 1b: Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]

  Baseline to Measured Progressive Disease (Up to 24 Months)

• Phase 1a and 1b: Duration of Response (DoR)

  Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 24 Months)

• Phase 1a and 1b: Time to First Response (TTR)

  Baseline to Date of CR or PR (Up to 24 Months)

• Phase 1a and 1b: Progression Free Survival (PFS)

  Baseline to PD or Death of Any Cause (Up to 24 Months)

Study Arms (7)

Cohort A

EXPERIMENTAL

Participants with gastroesophageal junction (GEJ) cancer \[Second-Third Line (L)\] received 8 milligrams per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 for every 3 weeks (Q3W) of a 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab

Cohort A1

EXPERIMENTAL

Participants with BTC cancer (Second-Third L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Drug: Ramucirumab

Cohort A2

EXPERIMENTAL

Participants with Gastric-GEJ cancer (First L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab

Cohort B

EXPERIMENTAL

Participants with Gastric-GEJ cancer (Second-Third L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab

Cohort C

EXPERIMENTAL

Participants with NSCLC (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab

Cohort D

EXPERIMENTAL

Participants with Urothelial cancer (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab

Cohort E

EXPERIMENTAL

Participants with NSCLC cancer (First L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab

Interventions

Ramucirumab DRUG

Administered IV

Also known as: LY3009806, IMC-1121B, Cyramza

Cohort A; Cohort A1; Cohort A2; Cohort B; Cohort C; Cohort D; Cohort E

Pembrolizumab DRUG

Administered IV

Also known as: MK3475

Cohort A; Cohort A2; Cohort B; Cohort C; Cohort D; Cohort E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (22)

Yale University School of Medicine

New Haven, Connecticut, 06520-8020, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists and Research Institute

St. Petersburg, Florida, 33705, United States

Location

Tennessee Oncology PLLC

Chattanooga, Tennessee, 37404, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Dijon, 21034, France

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Lille, 59020, France

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Lyon, 69373, France

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Paris, 75248, France

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Dresden, 01307, Germany

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Heidelberg, 69126, Germany

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Tübingen, 72076, Germany

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Kochi, 780-0051, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Yamanashi, 400-0124, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Barcelona, 08035, Spain

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Madrid, 28050, Spain

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Pamplona, 31008, Spain

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

London, W1G 6AD, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Manchester, M20 4BX, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 33068794 DERIVED

• 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.

  PMID: 31301962 DERIVED

• 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.

  PMID: 29853658 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Biliary Tract Neoplasms; Urinary Bladder Neoplasms; Urethral Neoplasms; Ureteral Neoplasms

Interventions

Ramucirumab; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Urethral Diseases; Ureteral Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: July 29, 2015
• Primary Completion: August 31, 2018
• Study Completion: April 12, 2022
• Last Updated: July 31, 2024
• Results First Posted: July 31, 2024

Record last verified: 2024-02

Locations

US (7); JP (2); ES (3); GB (3); DE (3); FR (4)