A Study of BMS-986148 in Patients With Select Advanced Solid Tumors

NCT02341625 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CA008-0022014-002485-70
• Study Type: interventional
• Target: 126
• Locations: 7 countries
• Sites: 17

Brief Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity and pharmacodynamics of BMS-986148 administered alone and in combination with nivolumab in patients with mesothelioma, non-small cell lung cancer, ovarian cancer, pancreatic cancer and gastric cancer.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events at Worst CTC Grade

  Number of participants with adverse events at worst CTC grade including any grade adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuations, and deaths grouped by dose + dose regimen.

  From first dose to up to 100 days post last dose (Up to 6 months)

• Number of Participants With Laboratory Test Toxicity Grade Shifting From Baseline

  Number of participants with laboratory test toxicity grade (Grade 0, 1, 2, 3, and 4) in hematology and chemistry shifting from baseline. An increase in baseline indicates a shift of participant to a greater toxicity grade. A decrease in baseline indicates a shift of participant to a lesser toxicity grade. Participants are grouped by dose + dose regimen assessed by NCT CTCAE V 4.03.

  From first dose to up to 100 days post last dose (Up to 6 months)

Secondary Outcomes (13)

• Maximum Observed Serum Concentration (Cmax)

  PK blood assessed on cycle 1, day 1

• Time of Maximum Observed Serum Concentration (Tmax)

  PK blood assessed on cycle 1, day 1

• Concentration at the End of a Dosing Interval (Ctau)

  PK blood assessed on cycle 1, day 1

• Trough Observed Serum Concentration (Ctrough)

  PK blood assessment include cycle 2-day 1 and cycle 1-day 8

• Area Under the Concentration-Time Curve From Time Zero to Time T (AUC(0-t))

  PK blood assessment include cycle 1-day 1

Study Arms (4)

Part 1: Ascending dose of BMS-986148

EXPERIMENTAL

BMS-986148 Intravenous injection at increasing doses on specific days until the maximum tolerated dose is reached. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer. Alternate dose and schedules may be explored.

Drug: BMS-986148

Part 2: Expansion dose of BMS-986148

EXPERIMENTAL

BMS-986148 Intravenous injection of Maximum tolerated dose (MTD) on specific days. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.

Drug: BMS-986148

Part 3A: Ascending dose of BMS-986148

EXPERIMENTAL

Set dose of nivolumab and BMS-986148 intravenous injection at increasing doses on specific days until the maximum tolerated dose is reached. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.

Drug: BMS-986148; Biological: Nivolumab

Part 3B: Expansion dose of BMS-986148

EXPERIMENTAL

Set dose of nivolumab and BMS-986148 intravenous injection at or below maximum tolerated dose on specific days. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.

Drug: BMS-986148; Biological: Nivolumab

Interventions

BMS-986148 DRUG

Part 1: Ascending dose of BMS-986148; Part 2: Expansion dose of BMS-986148; Part 3A: Ascending dose of BMS-986148; Part 3B: Expansion dose of BMS-986148

Nivolumab BIOLOGICAL

Also known as: Opdivo

Part 3A: Ascending dose of BMS-986148; Part 3B: Expansion dose of BMS-986148

Eligibility Criteria

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

You may qualify if:

• Must have pancreatic, ovarian, gastric, non-small cell cancer or mesothelioma. For dose expansion, must have tumor that is positive for mesothelin
• Expected to have life expectancy of at least 3 months
• Men and women 18 years old or older (or local age of majority)
• Must have measurable tumor per Response Evaluation Criteria In Solid Tumors (RECIST) or modified RECIST for malignant pleural mesothelioma
• ECOG of 0 to 1

You may not qualify if:

• Cancer metastases in the brain
• Moderate eye disorders
• Active infection or past hepatitis B or C infection
• Major surgery less than 1 month before the start of the study
• Uncontrolled heart disease
• Impaired liver or bone marrow function
• History of allergy to mesothelin-directed antibodies, tubulysin, monoclonal antibodies, nivolumab or related compounds

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (17)

Moores Cancer Center

La Jolla, California, 92093-0698, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Local Institution - 0013

Liverpool, New South Wales, 2170, Australia

Location

Local Institution - 0014

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 0004

Clayton, Victoria, 3168, Australia

Location

Local Institution - 0015

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0008

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Local Institution - 0009

Brussels, 1200, Belgium

Location

Local Institution - 0002

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0003

Toronto, Ontario, M5G 1Z5, Canada

Location

Local Institution - 0017

Milan, Lombardy, 20141, Italy

Location

Local Institution - 0018

Milan, 20133, Italy

Location

Local Institution - 0016

Rozzano (milano), 20089, Italy

Location

Local Institution - 0010

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0011

Rotterdam, 3015 AA, Netherlands

Location

Local Institution - 0007

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Local Institution - 0006

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

Related Publications (1)

• Rottey S, Clarke J, Aung K, Machiels JP, Markman B, Heinhuis KM, Millward M, Lolkema M, Patel SP, de Souza P, Duca M, Curigliano G, Santoro A, Koyama T, Brown M, Vezina H, He C, Chu QS. Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 Jan 1;28(1):95-105. doi: 10.1158/1078-0432.CCR-21-1181. Epub 2021 Oct 6.

  PMID: 34615718 DERIVED

Related Links

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

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: January 14, 2015
• First Posted: January 19, 2015
• Study Start: June 19, 2015
• Primary Completion: February 25, 2019
• Study Completion: May 7, 2020
• Last Updated: August 18, 2022
• Results First Posted: August 18, 2022

Record last verified: 2022-07

Locations

IT (3); GB (2); CA (2); BE (2); NL (2); US (2); AU (4)