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

Lilly

Status and phase: Completed; Phase 1

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

Treatments: Drug: Ramucirumab; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02443324

2015-001473-40 (EudraCT Number)

KEYNOTE -098 (Other Identifier)

15787

I4T-MC-JVDF (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 175 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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175 participants in 7 patient groups

Cohort A

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Ramucirumab

Cohort A1

Experimental group

Description:

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.

Treatment:

Drug: Ramucirumab

Cohort A2

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Ramucirumab

Cohort B

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Ramucirumab

Cohort C

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Ramucirumab

Cohort D

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Ramucirumab

Cohort E

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Ramucirumab