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

Eli Lilly and Company175 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

175

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Cycle 1 (21 Days)

Secondary Outcomes

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

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Time frame: 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)]

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. Participants who do not have any postbaseline tumor response assessments for any reason were considered.

Time frame: Baseline to Measured Progressive Disease (Up to 24 Months)

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

The duration of response is defined only for responders (patients with a confirmed CR or PR). It is measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, DoR will be censored at the date of the last complete objective progression-free disease assessment (CR or PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause.

Time frame: 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)

TTR is defined as the time from the date of first study treatment until the first evidence of a confirmed CR or PR.

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

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

PFS is defined as the time from the date of first study treatment until the date of the first observed radiographically documented progressive disease (PD) or death due to any cause, whichever is earlier. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.

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

Phase 1a and 1b: Overall Survival (OS)

The OS time is defined as the time from baseline to the date of death from any cause. If a participant is not known to have died on or before the date of data cut-off, OS data will be censored on the last date (on or before the cut-off date) the participant was known to be alive.

Time frame: Baseline to Death from Any Cause (Up to 24 Months)

Phase 1a and 1b: Pharmacokinetics (PK): Minimum Trough Concentration (Cmin) of Ramucirumab

PK: Cmin of Ramucirumab following administration every 3 weeks.

Time frame: Phase 1a (Gastric-GEJ or BTC participants (pts)): Week (Wk) 1, 3, 6 and 9; Phase 1a (Gastric, NSCLC, or urothelial pts): Wk 3, 6, 9 and 12; Cohort A, A1, A2: Wk 1, 3, 6, 9, 12, 18, 19 and 24; Cohort B,C,D,E: Wk 3, 6, 9, 12, 18, 19 and 24