NCT02443324 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2024-07-31

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Drug: Ramucirumab
Drug: Pembrolizumab
label
Cohort A
type
EXPERIMENTAL
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.
intervention Names
Drug: Ramucirumab
label
Cohort A1
type
EXPERIMENTAL
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.
intervention Names
Drug: Ramucirumab
Drug: Pembrolizumab
label
Cohort A2
type
EXPERIMENTAL
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.
intervention Names
Drug: Ramucirumab
Drug: Pembrolizumab
label
Cohort B
type
EXPERIMENTAL
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.
intervention Names
Drug: Ramucirumab
Drug: Pembrolizumab
label
Cohort C
type
EXPERIMENTAL
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.
intervention Names
Drug: Ramucirumab
Drug: Pembrolizumab
label
Cohort D
type
EXPERIMENTAL
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.
intervention Names
Drug: Ramucirumab
Drug: Pembrolizumab
label
Cohort E
type
EXPERIMENTAL

interventions

arm Group Labels
Cohort A
Cohort A1
Cohort A2
Cohort B
Cohort C
Cohort D
Cohort E
description
Administered IV
name
Ramucirumab
other Names
LY3009806
IMC-1121B
Cyramza
type
DRUG
arm Group Labels
Cohort A
Cohort A2
Cohort B
Cohort C
Cohort D
Cohort E
description
Administered IV
name
Pembrolizumab
other Names
MK3475
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 175
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Phase 1a: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
time Frame
Cycle 1 (21 Days)

secondary Outcomes

description
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.
measure
Phase 1a and 1b: Percentage 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 (Up to 24 Months)
description
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.
measure
Phase 1a and 1b: Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]
time Frame
Baseline to Measured Progressive Disease (Up to 24 Months)
description
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.
measure
Phase 1a and 1b: Duration of Response (DoR)
time Frame
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 24 Months)
description
TTR is defined as the time from the date of first study treatment until the first evidence of a confirmed CR or PR.
measure
Phase 1a and 1b: Time to First Response (TTR)
time Frame
Baseline to Date of CR or PR (Up to 24 Months)
description
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.
measure
Phase 1a and 1b: Progression Free Survival (PFS)
time Frame
Baseline to PD or Death of Any Cause (Up to 24 Months)
description
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.
measure
Phase 1a and 1b: Overall Survival (OS)
time Frame
Baseline to Death from Any Cause (Up to 24 Months)
description
PK: Cmin of Ramucirumab following administration every 3 weeks.
measure
Phase 1a and 1b: Pharmacokinetics (PK): Minimum Trough Concentration (Cmin) of Ramucirumab
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

Full study description

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).

Source references

references

citation
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
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED