A Dose Escalation and Combination Immunotherapy Study to Evaluate BMS-986226 Alone or in Combination With Nivolumab or Ipilimumab in Patients With Advanced Solid Tumors

NCT03251924 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CA021-0022017-000238-73
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 13

Brief Summary

The purpose of this study is to investigate BMS-986226 administered alone or in combination with nivolumab or ipilimumab.

Conditions

Cancer; Tumors; Neoplasm; Malignancy

Outcome Measures

Primary Outcomes (6)

• The Number of Participants Experiencing 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 up to 100 days post last dose, up to approximately 31 months

• The Number of Participants Experiencing Serious Adverse Events (SAEs)

  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 up to 100 days post last dose, up to approximately 31 months

• The Number of Participants Experiencing Adverse Events (AEs) Meeting Dose Limiting Toxicity (DLT) Criteria

  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. Dose limiting toxicity (DLT) is defined based on the incidence, intensity, and duration of AEs for which no clear alternative cause is identified. The DLT period will be 28 days (4 weeks) in the Preliminary Safety Cohorts. Any toxicities that occur beyond the 4-week DLT period will also be considered in dose-level decisions. For the purpose of participant management, any AE that meets DLT criteria, regardless of the cycle in which it occurs, will lead to discontinuation of study treatment. AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

  From first dose up to 100 days post last dose, up to approximately 31 months

• The Number of Participants Experiencing Adverse Events 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 up to 100 days post last dose, up to approximately 31 months

• The Number of Participants Experiencing Adverse Events Resulting in 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.

  From first dose up to 100 days post last dose, up to approximately 31 months

• The Number of Participants Experiencing Clinical Laboratory Abnormalities

  The number of participants experiencing abnormal laboratory results of Grade 3 or higher. Laboratory values will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with Grade 3=severe and Grade 4=life threatening.

  From first dose up to 30 days post last dose (approximately 28 months)

Secondary Outcomes (17)

• Objective Response Rate (ORR)

  From first dose up to documented disease progression, up to 48 months

• Median Duration of Response (DOR)

  From first dose up to the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 24 months)

• Progression Free Survival (PFS) Rate at 24 Weeks

  At 24 weeks

• Number of Participants With Anti-Drug Antibodies (ADA) for BMS-986226

  Predose on cycles 1-6, post dose on C1D15, and 30, 60, and 100 days post last dose (up to approximately 31 months)

• Changes From Baseline in Cell Surface ICOS Expression on T Cells

  From baseline up to pre-dose and 4 hours post dose on C1D1 and pre-dose and 4 hours post dose on C2D1 (approximately 31 months)

Study Arms (3)

BMS-986226

EXPERIMENTAL

administered intravenously

Drug: BMS-986226; Biological: Tetanus Vaccine

BMS-986226 and Nivolumab

EXPERIMENTAL

administered intravenously

Drug: BMS-986226; Biological: Nivolumab; Biological: Tetanus Vaccine

BMS-986226 and Ipilimumab

EXPERIMENTAL

administered intravenously

Drug: BMS-986226; Biological: Ipilimumab; Biological: Tetanus Vaccine

Interventions

BMS-986226 DRUG

specified dose on specified days

BMS-986226; BMS-986226 and Ipilimumab; BMS-986226 and Nivolumab

Nivolumab BIOLOGICAL

specified dose on specified days

Also known as: BMS-936558, PD-1 receptor blocking monoclonal antibody [mAb], Opdivo

BMS-986226 and Nivolumab

Ipilimumab BIOLOGICAL

specified dose on specified days

Also known as: BMS-734016, MDX010, Checkpoint blocking antibody that recognizes CTLA-4, Yervoy

BMS-986226 and Ipilimumab

Tetanus Vaccine BIOLOGICAL

specified dose on specified days

BMS-986226; BMS-986226 and Ipilimumab; BMS-986226 and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced solid tumors
• Histological or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or PCWG3 (prostate only).
• At least 1 lesion accessible for biopsy in addition to the target lesion
• Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2

You may not qualify if:

• Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded (controlled brain metastases will be allowed to enroll)
• Participants with carcinomatous meningitis
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
• Active, known, or suspected autoimmune disease
• Uncontrolled or significant cardiovascular disease
• Participants with known allergies to egg products, neomycin and tetanus toxoid.
• Prior adverse reaction to tetanus toxoid- containing vaccines.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (13)

Local Institution - 0005

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0012

St Louis, Missouri, 63110, United States

Location

Local Institution - 0002

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0001

Philadelphia, Pennsylvania, 19111, United States

Location

Local Institution - 0004

Nashville, Tennessee, 37203, United States

Location

Local Institution - 0014

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0006

Hamilton, Ontario, L8V 5C2, Canada

Location

Local Institution - 0003

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0007

Madrid, 28040, Spain

Location

Local Institution - 0008

Madrid, 28050, Spain

Location

Local Institution - 0009

Chur, 7000, Switzerland

Location

Local Institution - 0010

Lausanne, 1011, Switzerland

Location

Local Institution - 0011

Zurich, 8091, Switzerland

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasms

Interventions

Nivolumab; Ipilimumab; Tetanus Toxoid

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Toxoids; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

Study CA021002 was terminated because the Sponsor discontinued further development of BMS-986226. The decision for the study closure was not related to any safety concerns associated with BMS-986226.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2017
• First Posted: August 16, 2017
• Study Start: September 1, 2017
• Primary Completion: December 20, 2021
• Study Completion: December 20, 2021
• Last Updated: February 28, 2023
• Results First Posted: February 28, 2023

Record last verified: 2023-01

Locations

ES (2); CH (3); CA (3); US (5)