An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread

NCT02737475 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA012-0042015-004816-39
• Study Type: interventional
• Target: 166
• Locations: 6 countries
• Sites: 22

Brief Summary

The purpose of the study is to determine the safety and tumor-shrinking ability of experimental medication BMS-986178, when given by itself or in combination with Nivolumab and/or Ipilimumab, in participants with solid cancers that are advanced or have spread.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (8)

• The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

  The number of participants experiencing dose-limiting toxicities (DLTs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. DLTs are defined based on the incidence, severity, and duration of adverse events (AEs) for which no clear alternative cause is identified. 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 drug and that does not necessarily have a causal relationship with this treatment.

  From first dose to 28 days after first dose

• The Number of Participants Experiencing Adverse Events (AEs)

  The number of participants experiencing adverse events (AEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. 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 drug and that does not necessarily have a causal relationship with this treatment.

  From first dose to 100 days after last dose (up to approximately 2.5 years)

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

  The number of participants experiencing serious adverse events (SAEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. A SAE is 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, and/or is an important medical event.

  From first dose to 100 days after last dose (up to approximately 2.5 years)

• The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

  The number of participants experiencing adverse events (AEs) leading to discontinuation of study drug to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. 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 drug and that does not necessarily have a causal relationship with this treatment.

  From first dose to 100 days after last dose (up to approximately 2.5 years)

• The Number of Participant Deaths

  The number of deaths in each arm to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors.

  From first dose to study completion (up to approximately 4 years 5 months)

• The Number of Participants With Clinical Laboratory Test Abnormalities (Hematology)

  The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time

  From baseline to 100 days after last dose (up to approximately 2.5 years)

• The Number of Participants With Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION)

  The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time

  From baseline to 100 days after last dose (up to approximately 2.5 years)

• The Number of Participants With Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING )

  The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time

  From baseline to 100 days after last dose (up to approximately 2.5 years)

Secondary Outcomes (21)

• Objective Response Rate (ORR)

  From baseline up to approximately 2.5 years

• Duration of Response (DOR)

  From baseline up to approximately 2.5 years

• Progression Free Survival (PFS) Rate at 24 Weeks

  24 weeks after first dose

• Cmax: Maximum Observed Serum Concentration

  Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

• Tmax: Time of Maximum Observed Serum Concentration

  Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

Study Arms (9)

Part 1: Dose Escalation

EXPERIMENTAL

* BMS-986178 at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178

Part 2: Dose Escalation and Expansion

EXPERIMENTAL

* BMS-986178 in combination with Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Nivolumab

Part 3: Dose Escalation and Expansion

EXPERIMENTAL

* BMS-986178 in combination with Ipilimumab at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Ipilimumab

Part 4: Dose Schedule and Exploration

EXPERIMENTAL

* BMS-986178/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Nivolumab

Part 5: Dose Schedule and Exploration

EXPERIMENTAL

* BMS-986178/Ipilimumab at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Ipilimumab

Part 6: Dose Safety and Expansion

EXPERIMENTAL

* BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Nivolumab; Drug: Ipilimumab

Part 7: Dose Safety and Expansion

EXPERIMENTAL

* BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Nivolumab; Drug: Ipilimumab

Part 8: Dose Exploration

EXPERIMENTAL

* BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval * Enrollment is closed for this arm

Drug: BMS-986178; Drug: Nivolumab; Biological: Tetanus vaccine

Part 9: Dose Exploration

EXPERIMENTAL

* BMS-986178/Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 1) at specified doses at specified intervals OR Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 2) at specified doses at specified intervals * Enrollment is open for this arm \[Tumor type triple negative breast cancer (TNBC)\]

Drug: BMS-986178; Drug: Nivolumab; Biological: DPV-001 vaccine; Drug: Cyclophosphamide

Interventions

BMS-986178 DRUG

Specified dose on specified days

Part 1: Dose Escalation; Part 2: Dose Escalation and Expansion; Part 3: Dose Escalation and Expansion; Part 4: Dose Schedule and Exploration; Part 5: Dose Schedule and Exploration; Part 6: Dose Safety and Expansion; Part 7: Dose Safety and Expansion; Part 8: Dose Exploration; Part 9: Dose Exploration

Nivolumab DRUG

Specified dose on specified days

Also known as: BMS-936558, Opdivo

Part 2: Dose Escalation and Expansion; Part 4: Dose Schedule and Exploration; Part 6: Dose Safety and Expansion; Part 7: Dose Safety and Expansion; Part 8: Dose Exploration; Part 9: Dose Exploration

Ipilimumab DRUG

Specified dose on specified days

Also known as: BMS-734016, Yervoy

Part 3: Dose Escalation and Expansion; Part 5: Dose Schedule and Exploration; Part 6: Dose Safety and Expansion; Part 7: Dose Safety and Expansion

Tetanus vaccine BIOLOGICAL

Specified dose on specified days

Part 8: Dose Exploration

DPV-001 vaccine BIOLOGICAL

DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days

Part 9: Dose Exploration

Cyclophosphamide DRUG

Specified dose on specified days

Part 9: Dose Exploration

Eligibility Criteria

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

You may qualify if:

• For Part 9 (only arm open for enrollment):
• Stage IV metastatic or unresectable triple negative breast cancer (TNBC) with zero or one prior systemic therapies in the advanced metastatic setting
• Participants with \< 12 months from receipt of last curative-intent chemotherapy are allowed; curative chemotherapy will be considered first-line therapy
• Prior receipt of chemotherapy in the (neo)adjuvant setting is acceptable, as long as completed greater than 6 months from start of treatment
• Tumor biopsy samples (mandatory pre- and on-treatment biopsies) are required for all participants enrolled
• Must have histologic or cytologic confirmation of a malignancy that is advanced (metastatic, recurrent, refractory, and/or unresectable) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Men and women must agree to follow specific methods of contraception, if applicable

You may not qualify if:

• Must be immunotherapy treatment naïve, including no prior therapy with T cell immune checkpoint blocker (anti-PDL1, anti-PD1). Prior receipt of intralymphatic cytokine therapy (IRX-2) is acceptable (Part 9 only)
• Other active malignancy requiring concurrent intervention
• Prior therapy with any agent specifically targeting T-cell co-stimulation pathways such as anti-OX40 antibody, anti-CD137, anti- glucocorticoid-induced TNFR-related gene (anti-GITR) antibody, and anti-CD27
• Known or underlying medical or psychiatric condition and/or social reason that, in the opinion of the investigator or Sponsor, could make the administration of study drug hazardous to the participant or could adversely affect the ability of the participant to comply with or tolerate the study

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (22)

University Of Colorado

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center (Cumc)

New York, New York, 10032, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution

Ottawa, Ontario, K1H 8L6, Canada

Location

Local Institution

Toronto, Ontario, M5G 1Z5, Canada

Location

Local Institution

Ramat Gan, 52621, Israel

Location

Local Institution

Tel Aviv, 64239, Israel

Location

IRCCS Istituto Nazionale Tumori Milano

Milan, 20133, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Local Institution

Amsterdam, 1066 CX, Netherlands

Location

Local Institution

Utrecht, 3584 CX, Netherlands

Location

H. Univ. Vall dHebron

Barcelona, 08035, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28049, Spain

Location

Hosp. Univ. Puerta De Hierro

Majadahonda - Madrid, 28222, Spain

Location

Hospital Universitario Virgen De La Victoria

Málaga, 29010, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Related Publications (1)

• Gutierrez M, Moreno V, Heinhuis KM, Olszanski AJ, Spreafico A, Ong M, Chu Q, Carvajal RD, Trigo J, Ochoa de Olza M, Provencio M, De Vos FY, De Braud F, Leong S, Lathers D, Wang R, Ravindran P, Feng Y, Aanur P, Melero I. OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Clin Cancer Res. 2021 Jan 15;27(2):460-472. doi: 10.1158/1078-0432.CCR-20-1830. Epub 2020 Nov 4.

  PMID: 33148673 DERIVED

Related Links

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

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Tetanus Toxoid; Cyclophosphamide

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2016
• First Posted: April 14, 2016
• Study Start: June 17, 2016
• Primary Completion: November 2, 2020
• Study Completion: November 2, 2020
• Last Updated: January 25, 2022
• Results First Posted: January 25, 2022

Record last verified: 2021-12

Locations

US (8); CA (3); IL (2); IT (2); NL (2); ES (5)