Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0VYGGK
ADC Name
BMS-986148
Synonyms
BMS-986148
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Organization
Bristol-Myers Squibb (Top20 MNC) (Originator)
Drug Status
Phase 1/2 (discontinued)
Drug-to-Antibody Ratio
3
Structure
Antibody Name
BMS-986021
  Antibody Info 
Antigen Name
Mesothelin (MSLN)
  Antigen Info 
Payload Name
Tubulysin
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Mc-Val-Cit
  Linker Info 
Conjugate Type
Random Cysteines
The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
Indication Phase 1 Phase 1/2 Phase 2 Phase 2/3 Phase 3 New Drug Application Approved
Gastric cancer
1 Trials
Trial ID
NCT02341625; EudraCT2014-002485-70
Ovarian cancer
1 Trials
Trial ID
NCT02341625; EudraCT2014-002485-70
Pancreatic cancer
1 Trials
Trial ID
NCT02341625; EudraCT2014-002485-70
Pleura mesothelioma
1 Trials
Trial ID
NCT02341625; EudraCT2014-002485-70
Unspecific solid tumor
1 Trials
Trial ID
NCT02884726; jRCT2080223357; JapicCTI-163412
1 Trials
Trial ID
NCT02341625; EudraCT2014-002485-70
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 24 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 2.6 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.4 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 15.8 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.8 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 27.6 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.2 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 40 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.6 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 16.8 ug/mL
BMS-986148 + nivolumab every 3 week, Cycle 1, 0.8 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 8.8 ug/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.4 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 13.6 ug/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.6 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 16.1 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 0.8 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 25.3 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.2 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 24.7 ug/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.6 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 16 ug/mL
BMS-986148 + nivolumab every 3 week, Cycle 4, 0.8 mg/kg.
 [1]
Maximum Observed Concentration (Cmax) 6.74 ug/mL
BMS-986148 monotherapy once weekly, Cycle 4, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 372 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1093 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2304 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 3238 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1320 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.66 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1028 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1283 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2377 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1851 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1671 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 680 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 4, 0.4 mg/kg.
 [1]
Distribution
Click To Hide/Show 12 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 372 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1093 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2304 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 3238 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1320 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.66 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1028 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1283 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2377 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1851 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1671 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 680 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 4, 0.4 mg/kg.
 [1]
Metabolism
Click To Hide/Show 12 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 372 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1093 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2304 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 3238 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1320 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.66 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1028 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1283 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2377 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1851 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1671 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 680 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 4, 0.4 mg/kg.
 [1]
Excretion
Click To Hide/Show 12 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 372 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1093 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2304 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 3238 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 1, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1320 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 1, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.66 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.4 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1028 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 1, 0.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1283 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 2377 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.2 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1851 ug*h/mL
BMS-986148 monotherapy every 3 weeks, Cycle 4, 1.6 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 1671 ug*h/mL
BMS-986148 + nivolumab every 3 week, Cycle 4, 0.8 mg/kg.
 [1]
Area Under the Concentration-Time Curve (AUC) 680 ug*h/mL
BMS-986148 monotherapy once weekly, Cycle 4, 0.4 mg/kg.
 [1]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 5 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Objective Response Rate (ORR)  NCT02341625
Phase 1/2a
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
Undisclosed  NCT02341625
Phase 1/2
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
Undisclosed  NCT02884726
Phase 1
A phase 1 study of the safety and tolerability of BMS 986148 in subjects with advanced and/or metastatic solid tumors.
Objective Response Rate (ORR)  NCT02341625
PHASE1|||PHASE2
A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
Undisclosed  NCT02884726
PHASE1
A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
2.00
6.00
4.00
9.00
20.00
23.00 %
Patients Enrolled
Pleural or peritoneal mesothelioma (except sarcomatoid mesothelioma), ovarian cancer (except mucinous carcinoma), pancreatic cancer, gastric cancer, or non-small cell lung cancer (adenocarcinoma only).
Administration Dosage
BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability.
Related Clinical Trial
NCT Number NCT02341625  Clinical Status Phase 1/2a
Clinical Description A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
Primary Endpoint
The MTD and the recommended dose for the part 2 monotherapy expansion is BMS-986148 1.20 mg/kg every 3 weeks dose level. The MTD in the combination expansion cohort is BMS-986148 0.80 mg/kg + nivolumab 360 mg every 3 weeks.
Experiment 2 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT02341625  Clinical Status Phase 1/2
Clinical Description A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
Experiment 3 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT02884726  Clinical Status Phase 1
Clinical Description A phase 1 study of the safety and tolerability of BMS 986148 in subjects with advanced and/or metastatic solid tumors.
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Objective Response Rate (ORR)
9%
Patients Enrolled
Eligible participants (&ge;18 years, ECOG 0-1) must have mesothelin-positive measurable tumors (pancreatic/ovarian/gastric/NSCLC/mesothelioma) and &ge;3-month life expectancy. Exclusions cover brain metastases, active/hepatitis infections, major surgery (<1 month), uncontrolled cardiac/liver/bone marrow dysfunction, or hypersensitivity to mesothelin antibodies/tubulysin/nivolumab-related agents.

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Administration Dosage
.
Related Clinical Trial
NCT Number NCT02341625  Clinical Status PHASE1|||PHASE2
Clinical Description A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
Primary Endpoint
Safety outcomes include adverse events (AEs, SAEs, discontinuations, deaths) and laboratory toxicity shifts (hematology/chemistry) from baseline to 100 days post-treatment (≤6 months), analyzed by NCT CTCAE v4.03 criteria and grouped by dose/regimen.
Other Endpoint
Pharmacokinetics (Cmax, Tmax, Ctau, Ctrough, AUC (0-t), AUC[TAU]) are assessed during Cycle 1, with arithmetic %CV reported. Efficacy endpoints (up to 58 months) include best overall response (CR/PR/SD/PD), ORR, duration of response (DoR), progression-free survival (PFS), and PFS rates (4-12 months), stratified by tumor type (mesothelioma, pancreatic, ovarian, NSCLC, gastric). QTcF interval changes and ADA status are also evaluated by dose/regimen.

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Experiment 5 Reporting the Activity Date of This ADC [6]
Patients Enrolled
Eligible participants must have advanced/metastatic mesothelin-expressing solid tumors, progression/intolerance to standard therapy, measurable disease per RECIST, and ECOG 0-1. Exclusions include brain metastases, uncontrolled cardiovascular disease, eye/peripheral neuropathy, hepatitis B/C infection, or other protocol-specified conditions.
Administration Dosage
Specified dose on specified days
Related Clinical Trial
NCT Number NCT02884726  Clinical Status PHASE1
Clinical Description A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors
Primary Endpoint
Safety analysis covers adverse events (AEs/SAEs), including discontinuations and deaths, from Day 1 to 30 days post-treatment, with grading and laboratory toxicity shifts from baseline as key metrics for participant safety assessment.
Other Endpoint
Pharmacokinetic parameters (Cmax, Tmax, AUC (0-T), AUC (TAU), Ctrough, etc.) and accumulation indices (AI) are evaluated from Day 1 to 84, alongside tumor response based on RECIST criteria post-BMS-986148 treatment to assess drug exposure and efficacy.
References
Ref 1 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
Ref 2 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.
Ref 3 A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors, NCT02341625
Ref 4 A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors, NCT02884726
Ref 5 A Study of BMS-986148 in Patients With Select Advanced Solid Tumors
Ref 6 Phase 1 Study of Mesothelin-ADC