Gastric AdenocarcinomaPhase 1NCT02443324

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

A Phase 1 study testing Ramucirumab and Pembrolizumab in people with Gastric Adenocarcinoma and Adenocarcinoma of the Gastroesophageal Junction, run by Eli Lilly and Company at 22 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Gastric Adenocarcinoma, Adenocarcinoma of the Gastroesophageal Junction, Non-small Cell Lung Cancer
What is being tested?: Ramucirumab and Pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 175 participants
Where: 22 sitesin 6 countries
Study dates: 29 Jul 2015to 12 Apr 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 9Show fewer

Have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.
Has adequate organ function.
Have an anticipated life expectancy of ≥3 months.

Who cannot join

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.

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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 locations and contacts

22 sites in 6 countries.

Country

City, postcode or hospital

22 sites in 6 countries

United States7 sites

Tennessee Oncology PLLC
Chattanooga, Tennessee, 37404
Florida Cancer Specialists
Fort Myers, Florida, 33916
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, 37203
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Yale University School of Medicine
New Haven, Connecticut, 06520-8020
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Florida Cancer Specialists and Research Institute
St. Petersburg, Florida, 33705

Other trials in United States

France4 sites

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
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
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
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

Other trials in France

Germany3 sites

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
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
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

Other trials in Germany

Spain3 sites

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
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
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

Other trials in Spain

United Kingdom3 sites

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
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
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

Other trials in United Kingdom

Japan2 sites

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
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

Other trials in Japan

About this study

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

Conditions: Gastric Adenocarcinoma, Adenocarcinoma of the Gastroesophageal Junction, Non-small Cell Lung Cancer, Carcinoma, Transitional Cell, Biliary Tract Cancer
Being tested: Ramucirumab, Pembrolizumab
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
Medical subject headings: Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell, Biliary Tract Neoplasms, Urinary Bladder Neoplasms, Urethral Neoplasms, Ureteral Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RamucirumabDrug
Also called LY3009806, IMC-1121B, Cyramza
Administered IV
PembrolizumabDrug
Also called MK3475
Administered IV

Study groups in NCT02443324
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Ramucirumab; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)]
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Jul 201512 Apr 2022

First posted13 May 2015 (estimated)
Study start29 Jul 2015
Primary completion31 Aug 2018
Study completion12 Apr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 175 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02443324
Sponsor's protocol ID: 15787
Other IDs: I4T-MC-JVDF, 2015-001473-40, KEYNOTE -098, 2015
Status last verified: Feb 2024
First submitted: 11 May 2015
Last updated: 31 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 33068794
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.
PubMed 31301962
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.
PubMed 29853658

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingPhase 2
Perioperative Chemotherapy With Low-Dose Radiotherapy and Tislelizumab for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
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All Gastric Adenocarcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02443324
Acronym / sponsor ID: 15787
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
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 175 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Collaborators: Merck Sharp & Dohme LLC
Study start: 29 Jul 2015 (actual)
Primary completion: 31 Aug 2018 (actual)
Study completion: 12 Apr 2022 (actual)
First posted: 13 May 2015 (estimated)
Results: Posted 31 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 7

Arm	Type	Receives
Cohort A	Experimental	Drug: Ramucirumab, Drug: PembrolizumabParticipants 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.
Cohort A1	Experimental	Drug: RamucirumabParticipants 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.
Cohort A2	Experimental	Drug: Ramucirumab, Drug: PembrolizumabParticipants 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.
Cohort B	Experimental	Drug: Ramucirumab, Drug: PembrolizumabParticipants 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.
Cohort C	Experimental	Drug: Ramucirumab, Drug: PembrolizumabParticipants 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.
Cohort D	Experimental	Drug: Ramucirumab, Drug: PembrolizumabParticipants 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.
Cohort E	Experimental	Drug: Ramucirumab, Drug: PembrolizumabParticipants 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Metastatic disease or locally advanced, unresectable disease.
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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RamucirumabAlso: LY3009806, IMC-1121B, CyramzaAdministered IV	Drug	Cohort A, Cohort A1, Cohort A2, Cohort B, Cohort C, Cohort D, Cohort E
PembrolizumabAlso: MK3475Administered IV	Drug	Cohort A, Cohort A2, Cohort B, Cohort C, Cohort D, Cohort E

Primary outcome

Phase 1a: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 (21 Days)
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.

7 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)]
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)]
Time frame: Baseline to Measured Progressive Disease (Up to 24 Months)
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)
Phase 1a and 1b: Time to First Response (TTR)
Time frame: Baseline to Date of CR or PR (Up to 24 Months)
Phase 1a and 1b: Progression Free Survival (PFS)
Time frame: Baseline to PD or Death of Any Cause (Up to 24 Months)
Phase 1a and 1b: Overall Survival (OS)
Time frame: Baseline to Death from Any Cause (Up to 24 Months)
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

Results and safety

Results posted to the registry on 31 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A	24	0
Cohort A1	26	1
Cohort A2	29	4
Cohort B	17	1
Cohort C	28	7
Cohort D	24	0
Cohort E	27	8

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

Time frame: Cycle 1 (21 Days). Number. Unit: participants

Measure	Cohort A n = 6	Cohort C n = 3
Value	1	0

Population analysed: All enrolled participants who received at least one dose of the study drug in dose escalation phase and experienced a DLT. DLT was assessed in Phase 1a of Cohorts A and C during Cycle 1.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline Up to 5.9 Years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A	10 of 24 (41.7%)	23 of 24 (95.8%)	21 of 24
Cohort A1	15 of 26 (57.7%)	26 of 26 (100%)	19 of 26
Cohort A2	16 of 28 (57.1%)	28 of 28 (100%)	17 of 28
Cohort B	10 of 17 (58.8%)	16 of 17 (94.1%)	13 of 17
Cohort C	15 of 27 (55.6%)	27 of 27 (100%)	16 of 27
Cohort D	16 of 24 (66.7%)	24 of 24 (100%)	18 of 24
Cohort E	14 of 26 (53.8%)	26 of 26 (100%)	9 of 26

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33068794Herbst 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.
Derived from this study: PubMed 31301962Herbst 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.
Derived from this study: PubMed 29853658Arkenau 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.
A Study of Ramucirumab Plus Pembrolizumab in Participants With Gastric or GEJ Adenocarcinoma, NSCLC, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract CancerLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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) study director

Eli Lilly and Company

22 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, France, Germany, Spain, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1a: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 Days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02443324, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2024.