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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02341625
First Posted: January 19, 2015
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Bristol-Myers Squibb
  Purpose
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.

Condition Intervention Phase
Advanced Cancer Drug: BMS-986148 Biological: Nivolumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety is measured by incidence of adverse events (AEs) at its worst grade, serious adverse events (SAEs) at its worst grade, adverse events leading to discontinuations, deaths, frequency of laboratory test toxicity grade shifting from baseline [ Time Frame: Approximately 5 years ]

Secondary Outcome Measures:
  • Maximum observed serum or plasma concentration (Cmax) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Time of maximum observed serum or plasma concentration (Tmax) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Concentration at the end of a dosing interval (Ctau) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Trough observed serum or plasma concentration (this includes pre-dose concentrations and Ctau concentrations) (Ctrough) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Area under the concentration-time curve from time 0 to time t (AUC(0-t)) of BMS-986148 (t= t last) [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Terminal serum or plasma half-life (T-Half) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Total body clearance calculated as Dose divided by AUC(TAU) (CLT) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Volume of distribution at steady-state (Vss) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Volume of distribution of terminal phase (Vz) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Accumulation index; ratio of Cmax at steady-state to Cmax after the first dose (AI_Cmax) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Accumulation index; ratio of Ctau at steady-state to Ctau after the first dose (AI_Ctau) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Average concentration over a dosing interval calculated by dividing AUC(TAU) by tau (Cavg) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
  • Best overall response (BOR) of BMS-986148 [ Time Frame: Approximately 5 years ]
    Best overall response (BOR): 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

  • Objective Response rate (ORR) [ Time Frame: Approximately 5 years ]
    Objective Response Rate (ORR): defined as the total number of patients whose best overall response (BOR) is either a Complete Response (CR) or Partical Response (PR) divided by the total number of patients in the population of interest

  • Duration of response [ Time Frame: Approximately 5 years ]
    Duration of Response: defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first

  • Progression free survival [ Time Frame: Approximately 5 years ]
    Duration of Response: defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first

  • Progression free survival rate [ Time Frame: Approximately 5 years ]
    Progression Free Survival Rate (PFSR) at week 't': defined as the proportion of patients who remain progression free and surviving at 't' weeks (t=12, 24, 36, etc)

  • Overall survival [ Time Frame: Approximately 5 years ]
    Overall Survival (OS): defined as the time between the date of first dose of study medication and the date of death

  • Overall survival rate [ Time Frame: Approximately 5 years ]
    Overall Survival Rate (OSR) at month 't': defined as the probability of patients surviving at 't' months (eg, t=6, 12, 24 months, etc)

  • Changes in QTcF of BMS-986148 [ Time Frame: Day 1 through day 7 and day 66 through day 73 ]
  • Immunogenicity of BMS-986148 [ Time Frame: Day 1 through day 100 ]
    Immunogenicity as measured by positive Anti-drug antibody (ADA)


Estimated Enrollment: 407
Actual Study Start Date: June 17, 2015
Estimated Study Completion Date: August 29, 2022
Estimated Primary Completion Date: June 14, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Ascending dose of BMS-986148
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
Experimental: Part 2: Expansion dose of BMS-986148
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
Experimental: Part 3A: Ascending dose of BMS-986148
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
Other Name: Opdivo
Experimental: Part 3B: Expansion dose of BMS-986148
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
Other Name: Opdivo

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02341625


Locations
United States, California
UC San Diego Moores Cancer Ctr
La Jolla, California, United States, 92093-0698
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Australia, New South Wales
Local Institution
Liverpool, New South Wales, Australia, 2170
Australia, South Australia
Local Institution
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Local Institution
Clayton, Victoria, Australia, 3168
Australia, Western Australia
Local Institution
Nedlands, Western Australia, Australia, 6009
Belgium
Local Institution
Gent, EAST Flanders, Belgium, 9000
Local Institution
Bruxelles, Belgium, 1200
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 1Z5
Italy
Local Institution
Milano, Italy, 20133
Istituto Europeo Di Oncologia
Milano, Italy, 20141
Istituto Clinico Humanitas
Rozzano (milano), Italy, 20089
Netherlands
Local Institution
Amsterdam, Netherlands, 1066 CX
Local Institution
Rotterdam, Netherlands, 3075 EA
United Kingdom
Local Institution
Southampton, Hampshire, United Kingdom, SO16 6YD
Local Institution
Glasgow, Lanarkshire, United Kingdom, G12 0YN
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02341625     History of Changes
Other Study ID Numbers: CA008-002
2014-002485-70 ( EudraCT Number )
First Submitted: January 14, 2015
First Posted: January 19, 2015
Last Update Posted: November 17, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Nivolumab
Antineoplastic Agents