A Study of Cabiralizumab Given With Nivolumab With and Without Chemotherapy in Patients With Advanced Pancreatic Cancer

A Phase 2 Study of Cabiralizumab (BMS-986227, FPA008) Administered in Combination With Nivolumab (BMS-936558) With and Without Chemotherapy in Patients With Advanced Pancreatic Cancer

The purpose of this study is to determine whether an investigational immuno-therapy, cabiralizumab in combination with nivolumab, with or without chemotherapy, is effective for the treatment of advanced pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Pancreatic Cancer
• Intervention / Treatment: Biological: Nivolumab; Drug: Leucovorin; Drug: Nab-paclitaxel; Drug: Onivyde; Drug: Fluorouracil; Drug: Gemcitabine; Drug: Irinotecan Hydrochloride; Biological: Cabiralizumab; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Actual): 205
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Local Institution - 0037
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0035
• Denmark
  • Herlev, Denmark, 2730
    • Local Institution - 0041
• Germany
  • Heidelberg, Germany, 69120
    • Local Institution - 0032
  • Mannheim, Germany, 68167
    • Local Institution - 0029
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
  • Wuerzburg, Germany, 97080
    • Local Institution - 0030
• Italy
  • Padova, Italy, Padova
    • Local Institution - 0025
  • Roma, Italy, 00168
    • Local Institution - 0026
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 2778577
      • Local Institution - 0023
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 1040045
      • Local Institution - 0022
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Local Institution - 0018
  • Seoul, Korea, Republic of, 06351
    • Local Institution - 0017
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0021
  • Madrid, Spain, 28007
    • Local Institution - 0019
  • Madrid, Spain, 28041
    • Local Institution - 0020
• Switzerland
  • Chur, Switzerland, 7000
    • Local Institution - 0033
  • Lausanne, Switzerland, 1011
    • Local Institution - 0034
• Taiwan
  • Taipei, Taiwan, 112
    • Local Institution - 0031
  • Taipei City, Taiwan, 100
    • Local Institution - 0024
• United Kingdom
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G12 0YN
      • Local Institution - 0016
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic in Rochester, Minnesota
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Los Angeles, California, United States, 90095
      • Local Institution - 0007
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - South
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0001
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Dana Farber Cancer Institute.
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0010
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 0005
    • New York, New York, United States, 10016
      • Local Institution - 0012
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0006
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0009
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology Chattanooga
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution - 0013
    • Houston, Texas, United States, 77030
      • Local Institution - 0011
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must have histological or cytological confirmed diagnosis of locally advanced or metastatic adenocarcinoma of the pancreas, which has progressed on or after one line of chemotherapy
• ECOG Performance status 0-1
• Adequate organ functions
• Measurable disease

Exclusion Criteria:

• Suspected or known CNS metastasis
• Participants with active, known, or suspected autoimmune disease
• Uncontrolled or significant cardiovascular disease
• Prior exposure to selected immune cell-modulating antibody regimens

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Investigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)	Drug: Leucovorin; Specified dose on specified days; Drug: Nab-paclitaxel; specified does on specified days; Other Names: Abraxane; Drug: Onivyde; specified dose on specified days; Other Names: irinotecan liposome; Drug: Fluorouracil; specified dose on specified days; Other Names: 5-Fluorouracil; Drug: Gemcitabine; specified dose on specified days; Drug: Irinotecan Hydrochloride; Specified dose on specified days
Experimental: Arm B; Cabiralizumab Q2W + Nivolumab Q4W	Biological: Nivolumab; specified dose on specified days; Other Names: Opdivo, BMS-936558; Biological: Cabiralizumab; specified dose on specified days; Other Names: BMS-986227, FPA008
Experimental: Arm C; Cabiralizumab Q2W + Nivolumab Q4W and Gemcitabine + Nab-Paclitaxel (Abraxane®) D1, 8 and 15 Q4W	Biological: Nivolumab; specified dose on specified days; Other Names: Opdivo, BMS-936558; Drug: Nab-paclitaxel; specified does on specified days; Other Names: Abraxane; Drug: Gemcitabine; specified dose on specified days; Biological: Cabiralizumab; specified dose on specified days; Other Names: BMS-986227, FPA008
Experimental: Arm D; Cabiralizumab Q2W + Nivolumab Q4W and Oxaliplatin/5-Flurouracil/Leucovorin (FOLFOX) Q2W	Biological: Nivolumab; specified dose on specified days; Other Names: Opdivo, BMS-936558; Drug: Leucovorin; Specified dose on specified days; Drug: Fluorouracil; specified dose on specified days; Other Names: 5-Fluorouracil; Biological: Cabiralizumab; specified dose on specified days; Other Names: BMS-986227, FPA008; Drug: Oxaliplatin; specified dose on specified day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by BICR	PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization date to the date of first objectively documented disease progression or death (up to approximately 65 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Investigator	PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization date to the date of first objectively documented disease progression or death (up to approximately 65 months)
Progression Free Survival Rate (PFSR) by BICR	Progression Free Survival Rates at 6, 9, and 12 months is defined as the percentage of participants who achieve PFS at 6, 9, and 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	At 6, 9, and 12 months
Progression Free Survival Rate (PFSR) by Investigator	Progression Free Survival Rates at 6, 9, and 12 months is defined as the percentage of participants who achieve PFS at 6, 9, and 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	At 6, 9, and 12 months
Objective Response Rate (ORR) by BICR	ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 65 months)
Objective Response Rate (ORR) by Investigator	ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 65 months)
Duration of Response (DOR) by BICR	DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 65 months)
Duration of Response (DOR) by Investigator	DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 65 months)
Overall Survival (OS)	OS is defined as the time from randomization to the date of death due to any cause. Based on Kaplan-Meier Estimates.	From randomization to the date of death to any cause (up to approximately 65 months)
Overall Survival Rates (OSR)	Overall survival at 6 months, 1 year, and 2 years is defined as the percentage of participants who are alive at 6 months, 1 year, and 2 years. Based on Kaplan-Meier Estimates.	At 6 months, 1 year, and 2 years
The Number of Participants With Adverse Events (AEs)	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.	From first dose to 100 days after last dose of study therapy (up to approximately 51 months)
The Number of Participants With Serious Adverse Events (SAEs)	A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	From first dose to 100 days after last dose of study therapy (up to approximately 51 months)
The Number of Participants With Adverse Events (AEs) Leading to Discontinuation	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.	From first dose to 100 days after last dose of study therapy (up to approximately 51 months)
The Number of Participants Who Died	The number of participants that died during the study.	From first dose to 150 days after last dose of study therapy (up to approximately 53 months)
The Number of Participants Who Experienced Abnormal Hepatic Tests	The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)	From first dose and 100 days after last dose of study therapy (up to approximately 51 months)
The Number of Participants With On-Treatment Laboratory Abnormalities in Specific Thyroid Tests	The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN) Upper Limit of Normal (ULN)	From first dose and 100 days after last dose of study therapy (up to approximately 51 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 8, 2017

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 21, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Immune Checkpoint Inhibitors; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Paclitaxel; Fluorouracil; Oxaliplatin; Nivolumab; Leucovorin; Irinotecan; Gemcitabine
• Other Study ID Numbers: CA025-006

Drug and device information, study documents

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