Clinical trial NCT02341625: A Study of BMS-986148 in Patients With Select Advanced Solid Tumors
Official title: A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2015-01-19
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Adverse Events at Worst CTC Grade
timeFrame: From first dose to up to 100 days post last dose (Up to 6 months)
measure: Number of Participants With Laboratory Test Toxicity Grade Shifting From Baseline
timeFrame: From first dose to up to 100 days post last dose (Up to 6 months)
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: PK blood assessed on cycle 1, day 1
measure: Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: PK blood assessed on cycle 1, day 1
measure: Concentration at the End of a Dosing Interval (Ctau)
timeFrame: PK blood assessed on cycle 1, day 1
measure: Trough Observed Serum Concentration (Ctrough)
timeFrame: PK blood assessment include cycle 2-day 1 and cycle 1-day 8
measure: Area Under the Concentration-Time Curve From Time Zero to Time T (AUC(0-t))
timeFrame: PK blood assessment include cycle 1-day 1
measure: Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
timeFrame: PK blood assessment include cycle 1-day 1
measure: Best Overall Response (BOR)
timeFrame: Up to 58 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 58 months
measure: Duration of Response (DoR)
timeFrame: Up to 58 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 58 months
measure: Progression Free Survival Rate (PFSR) at Week t
timeFrame: Total PFS assessed between 4 and 12 months, PFSR at months 4 and 6 to be reported
measure: Changes in QT Corrected by the Fridericia Formula (QTcF) From Baseline, at Selected Times
timeFrame: Up to 58 months
measure: Number of Participants With Anti-Drug Antibody (ADA)
timeFrame: Up to 58 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center
state: California
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Liverpool
country: Australia
facility: Local Institution - 0013
state: New South Wales
city: Adelaide
country: Australia
facility: Local Institution - 0014
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0004
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0015
state: Western Australia
city: Gent
country: Belgium
facility: Local Institution - 0008
state: Oost-Vlaanderen
city: Bruxelles
country: Belgium
facility: Local Institution - 0009
city: Edmonton
country: Canada
facility: Local Institution - 0002
state: Alberta
city: Toronto
country: Canada
facility: Local Institution - 0003
state: Ontario
city: Milan
country: Italy
facility: Local Institution - 0017
state: Lombardia
city: Milano
country: Italy
facility: Local Institution - 0018
city: Rozzano (milano)
country: Italy
facility: Local Institution - 0016
city: Amsterdam
country: Netherlands
facility: Local Institution - 0010
city: Rotterdam
country: Netherlands
facility: Local Institution - 0011
city: Southampton
country: United Kingdom
facility: Local Institution - 0007
state: Hampshire
city: Glasgow
country: United Kingdom
facility: Local Institution - 0006
state: Lanarkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.