A Study to Test Combination Treatments in Participants With Advanced Gastric Cancer (FRACTION-GC)

A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-ONcology Study in Participants With Advanced Gastric Cancer (FRACTION-Gastric Cancer)

The purpose of this study is to evaluate the preliminary efficacy, safety, and tolerability of Nivolumab in combination with Ipilimumab or other treatment therapies in participants with advanced gastric cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Biological: Relatlimab; Biological: BMS-986205; Drug: Rucaparib

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Randwick, Australia, 2031
    • Local Institution
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0035
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0033
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0021
    • Toronto,, Ontario, Canada, M4N 3M5
      • Local Institution - 0025
• Germany
  • Heidelberg, Germany, 69120
    • Local Institution - 0039
  • Leipzig, Germany, 04103
    • Local Institution - 0043
• Israel
  • Ramat Gan, Israel, 52621
    • Local Institution
  • Tel Aviv, Israel, 64239
    • Local Institution
• Italy
  • Milano, Italy, 20133
    • IRCCS Istituto Nazionale Tumori Milano
  • Lombardia
    • Milan, Lombardia, Italy, 20141
      • Local Institution - 0014
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution
  • Utrecht, Netherlands, 3584 CX
    • Local Institution
• Singapore
  • Singapore, Singapore, 169610
    • Local Institution - 0050
• Switzerland
  • Zuerich, Switzerland, 8091
    • Local Institution - 0042
  • Graubünden (de)
    • Chur, Graubünden (de), Switzerland, 7000
      • Local Institution - 0041
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States, 91010-3000
      • Local Institution - 0020
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0032
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Local Institution - 0036
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Medical Oncology - Davis Cancer Pavilion
    • Jacksonville, Florida, United States, 32224
      • Local Institution - 0038
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Local Institution - 0006
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0017
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 0003
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0001
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 0007
  • Oregon
    • Portland, Oregon, United States, 97225
      • Local Institution - 0002
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Local Institution - 0005
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inoperable, advanced or metastatic esophageal cancer (EC), gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma and have histologically confirmed predominant adenocarcinoma and/or squamous carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• At least 1 lesion with measurable disease

Exclusion Criteria:

• HER2-positive tumor and previously untreated with trastuzumab
• Suspected, known or progressive central nervous system metastases
• Other active malignancy requiring concurrent intervention
• Active, known or suspected autoimmune disease

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + BMS-986205	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: BMS-986205; Specified dose on specified days
Active Comparator: Nivolumab + Ipilimumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: Ipilimumab; Specified dose on specified days; Other Names: BMS-734016; Yervoy
Experimental: Nivolumab + Relatlimab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: Relatlimab; Specified dose on specified days; Other Names: BMS-986016
Experimental: Nivolumab + Rucaparib	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Drug: Rucaparib; Specified dose on specified days; Other Names: Rubraca
Experimental: Ipilimumab + Rucaparib	Biological: Ipilimumab; Specified dose on specified days; Other Names: BMS-734016; Yervoy; Drug: Rucaparib; Specified dose on specified days; Other Names: Rubraca
Experimental: Nivolumab + Ipilimumab + Rucaparib	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: Ipilimumab; Specified dose on specified days; Other Names: BMS-734016; Yervoy; Drug: Rucaparib; Specified dose on specified days; Other Names: Rubraca

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) by Investigator	ORR is the percent of participants whose best overall response (BOR) is complete response (CR) or partial response (PR). BOR is the best response from the start of the study treatment until objectively documented progression per RECIST v1.1 or subsequent anticancer therapy, whichever occurs first. CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Response Evaluation Criteria in Solid Tumors (RECIST) is a standard way to measure the response of a tumor to treatment. CR+PR, confidence interval based on Clopper and Pearson method.	From first dose of study treatment until progression or subsequent anticancer therapy, whichever occurs first (up to approximately 65 months)
Median Duration of Response (DOR)	Duration of Response (DOR) is the time between the date of first response and the date of first documented disease progression as determined by RECIST 1.1 or death due to any cause, whichever occurred first. Complete Response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Median computed using Kaplan -Meier method.	From first dose to date of first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 65 months)
Kaplan-Meier Analysis of Progression Free Survival Rate (PFSR) at 24 Weeks	The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Point estimates are derived from Kaplan-Meier analyses, the 95% CIs are derived from Greenwood formula.	24 weeks after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With AEs, SAEs, AEs Leading to Discontinuation, and Death	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.	From first dose to 100 days after last dose of study therapy (assessed up to approximately 30 months)
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests	The number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal.	From first dose to 100 days after last dose of study therapy (approximately 30 months)
Number of Participants With Laboratory Abnormalities in Specific Liver Tests	The number of participants with laboratory abnormalities in specific liver tests based on US conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal	From first dose to 100 days after last dose of study therapy (approximately 30 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Clovis Oncology, Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2016
• Primary Completion (Actual): May 11, 2022
• Study Completion (Actual): May 11, 2022

Study Registration Dates

• First Submitted: October 14, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (Estimated): October 17, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Immune Checkpoint Inhibitors; Nivolumab; Rucaparib; Ipilimumab; Linrodostat; Relatlimab
• Other Study ID Numbers: CA018-003; 2016-002807-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No