Please note the ANZCTR will be unattended from Friday 24 December 2021 for the holidays. The Registry will re-open on Monday 17 January 2022. Submissions and updates will not be processed during that time.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02341625




Registration number
NCT02341625
Ethics application status
Date submitted
14/01/2015
Date registered
19/01/2015
Date last updated
16/11/2021

Titles & IDs
Public title
A Study of BMS-986148 in Patients With Select Advanced Solid Tumors
Scientific title
A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
Secondary ID [1] 0 0
2014-002485-70
Secondary ID [2] 0 0
CA008-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BMS-986148
Other interventions - Nivolumab

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.

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.

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.

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.


Treatment: Drugs: BMS-986148


Other interventions: Nivolumab


Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Approximately 5 years
Secondary outcome [1] 0 0
Maximum observed serum or plasma concentration (Cmax) of BMS-986148
Timepoint [1] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [2] 0 0
Time of maximum observed serum or plasma concentration (Tmax) of BMS-986148
Timepoint [2] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [3] 0 0
Concentration at the end of a dosing interval (Ctau) of BMS-986148
Timepoint [3] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [4] 0 0
Trough observed serum or plasma concentration (this includes pre-dose concentrations and Ctau concentrations) (Ctrough) of BMS-986148
Timepoint [4] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [5] 0 0
Area under the concentration-time curve from time 0 to time t (AUC(0-t)) of BMS-986148 (t= t last)
Timepoint [5] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [6] 0 0
Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-986148
Timepoint [6] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [7] 0 0
Terminal serum or plasma half-life (T-Half) of BMS-986148
Timepoint [7] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [8] 0 0
Total body clearance calculated as Dose divided by AUC(TAU) (CLT) of BMS-986148
Timepoint [8] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [9] 0 0
Volume of distribution at steady-state (Vss) of BMS-986148
Timepoint [9] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [10] 0 0
Volume of distribution of terminal phase (Vz) of BMS-986148
Timepoint [10] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [11] 0 0
Accumulation index; ratio of Cmax at steady-state to Cmax after the first dose (AI_Cmax) of BMS-986148
Timepoint [11] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [12] 0 0
Accumulation index; ratio of Ctau at steady-state to Ctau after the first dose (AI_Ctau) of BMS-986148
Timepoint [12] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [13] 0 0
Average concentration over a dosing interval calculated by dividing AUC(TAU) by tau (Cavg) of BMS-986148
Timepoint [13] 0 0
Day 1 through day 21 and day 66 through day 87
Secondary outcome [14] 0 0
Best overall response (BOR) of BMS-986148 - 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
Timepoint [14] 0 0
Approximately 5 years
Secondary outcome [15] 0 0
Objective Response rate (ORR) - 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
Timepoint [15] 0 0
Approximately 5 years
Secondary outcome [16] 0 0
Duration of response - 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
Timepoint [16] 0 0
Approximately 5 years
Secondary outcome [17] 0 0
Progression free survival - 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
Timepoint [17] 0 0
Approximately 5 years
Secondary outcome [18] 0 0
Progression free survival rate - 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)
Timepoint [18] 0 0
Approximately 5 years
Secondary outcome [19] 0 0
Overall survival - Overall Survival (OS): defined as the time between the date of first dose of study medication and the date of death
Timepoint [19] 0 0
Approximately 5 years
Secondary outcome [20] 0 0
Overall survival rate - Overall Survival Rate (OSR) at month 't': defined as the probability of patients surviving at 't' months (eg, t=6, 12, 24 months, etc)
Timepoint [20] 0 0
Approximately 5 years
Secondary outcome [21] 0 0
Changes in QTcF of BMS-986148
Timepoint [21] 0 0
Day 1 through day 7 and day 66 through day 73
Secondary outcome [22] 0 0
Immunogenicity of BMS-986148 - Immunogenicity as measured by positive Anti-drug antibody (ADA)
Timepoint [22] 0 0
Day 1 through day 100

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



- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Liverpool
Recruitment hospital [2] 0 0
Local Institution - Adelaide
Recruitment hospital [3] 0 0
Local Institution - Clayton
Recruitment hospital [4] 0 0
Local Institution - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
Belgium
State/province [3] 0 0
Bruxelles
Country [4] 0 0
Belgium
State/province [4] 0 0
Gent
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Italy
State/province [7] 0 0
Milano
Country [8] 0 0
Italy
State/province [8] 0 0
Milan
Country [9] 0 0
Italy
State/province [9] 0 0
Rozzano (milano)
Country [10] 0 0
Netherlands
State/province [10] 0 0
Amsterdam
Country [11] 0 0
Netherlands
State/province [11] 0 0
Rotterdam
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Hampshire
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Lanarkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02341625
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02341625