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

Advanced Cancer Clinical Trial

Official title:

A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02341625
• Other study ID #: CA008-002
• Secondary ID: 2014-002485-70
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 19, 2015
• Est. completion date: May 7, 2020

Study information

• Verified date: July 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 126
• Est. completion date: May 7, 2020
• Est. primary completion date: February 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer

Intervention

Drug:
• BMS-986148

Biological:
• Nivolumab

Locations

Country	Name	City	State
Australia	Local Institution - 0014	Adelaide	South Australia
Australia	Local Institution - 0004	Clayton	Victoria
Australia	Local Institution - 0013	Liverpool	New South Wales
Australia	Local Institution - 0015	Nedlands	Western Australia
Belgium	Local Institution - 0009	Bruxelles
Belgium	Local Institution - 0008	Gent	Oost-Vlaanderen
Canada	Local Institution - 0002	Edmonton	Alberta
Canada	Local Institution - 0003	Toronto	Ontario
Italy	Local Institution - 0017	Milan	Lombardia
Italy	Local Institution - 0018	Milano
Italy	Local Institution - 0016	Rozzano (milano)
Netherlands	Local Institution - 0010	Amsterdam
Netherlands	Local Institution - 0011	Rotterdam
United Kingdom	Local Institution - 0006	Glasgow	Lanarkshire
United Kingdom	Local Institution - 0007	Southampton	Hampshire
United States	Duke University Medical Center	Durham	North Carolina
United States	Moores Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Maximum Observed Serum Concentration (Cmax)	Maximum observed serum concentration (Cmax) of BMS-986148 grouped by dose + dose regimen.; Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.	PK blood assessed on cycle 1, day 1
Secondary	Time of Maximum Observed Serum Concentration (Tmax)	Time of maximum observed serum concentration (Tmax) of BMS-986148 grouped by dose + dose regimen.	PK blood assessed on cycle 1, day 1
Secondary	Concentration at the End of a Dosing Interval (Ctau)	Concentration at the end of a dosing interval (Ctau) of BMS-986148 grouped by dose + dose regimen.; Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.	PK blood assessed on cycle 1, day 1
Secondary	Trough Observed Serum Concentration (Ctrough)	Trough observed serum concentration (Ctrough) of BMS-986148 grouped by dose + dose regimen.; Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.	PK blood assessment include cycle 2-day 1 and cycle 1-day 8
Secondary	Area Under the Concentration-Time Curve From Time Zero to Time T (AUC(0-t))	Area under the concentration-time curve from time Zero to time T (AUC(0-t)) of BMS-986148 grouped by dose + dose regimen.; Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.	PK blood assessment include cycle 1-day 1
Secondary	Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])	Area under the concentration-time curve in one dosing interval (AUC[TAU]) of BMS-986148 grouped by dose + dose regimen Note: The geometric CV was not calculated. Arithmetic % CV is reported instead	PK blood assessment include cycle 1-day 1
Secondary	Best Overall Response (BOR)	Best overall response is defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy.; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 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 on study. The sum must also demonstrate an absolute increase of at least 5 mm.; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Up to 58 months
Secondary	Objective Response Rate (ORR)	Objective response rate is defined as the total percentage of participants whose best overall response (BOR) is either a complete response or partial response divided by the total percentage of participants who are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 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.	Up to 58 months
Secondary	Duration of Response (DoR)	Duration of response is defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first. Participants are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).	Up to 58 months
Secondary	Progression Free Survival (PFS)	Progression Free Survival is defined as the time from the first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause. Progression is defined with at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. Participants who did not progress nor died will be censored on the date of their last tumor assessment. Participants are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).	Up to 58 months
Secondary	Progression Free Survival Rate (PFSR) at Week t	Progression free survival rate is defined as the proportion of participants who remain progression free and surviving at 't' weeks (t=4-12 months). The proportion will be calculated by the product-limit method (Kaplan-Meier estimate) which takes into account censored data. Participants are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).	Total PFS assessed between 4 and 12 months, PFSR at months 4 and 6 to be reported
Secondary	Changes in QT Corrected by the Fridericia Formula (QTcF) From Baseline, at Selected Times	Changes of participants in QT corrected by the fridericia formula (QTcF) Interval from baseline at <= 30 msec, >30 - <= 60 msec, and > 60 msec grouped by dose + dose regimen	Up to 58 months
Secondary	Number of Participants With Anti-Drug Antibody (ADA)	Number of participants with anti-drug antibody (ADA) status grouped by dose + dose regimen.; Data was not collected for this outcome measure.	Up to 58 months

External Links

•   BMS Clinical Trial Information
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