Clinical trial NCT03110107: First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors
Official title: Phase 1/2a First-In-Human Study of BMS-986218 Monoclonal Antibody Alone and in Combination With Nivolumab in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Keywords: BMS-986218
Nivolumab
Ipilimumab
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-04-12
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether BMS-986218 both by itself and in combination with Nivolumab is safe and tolerable in the treatment of advanced solid tumors.


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable)
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Participants must have received, and then progressed, relapsed, or been intolerant to at least 2 standard treatment regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, if such a therapy exists
* Advanced stage cutaneous melanoma who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-programmed cell death 1 (anti-PD-1) or anti-programmed death ligand 1 (anti-PD-L1) (For Part 2A)
* Non-small cell lung cancer (NSCLC) (adenocarcinoma or squamous cell carcinoma) who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-PD-1 or anti-PD-L1 (For Parts 2B \& 2C)
* Microsatellite Stable Colorectal Cancer (MSS CRC) who have received standard therapies with proven survival benefit (Part 2D)

Exclusion Criteria:

* Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded
* Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy
* Prior anti-cancer treatments such as chemotherapy, radiotherapy, hormonal, or immunotherapy (including anti-PD-1/PD-L1) are permitted

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
measure: Number of Participants With Adverse Events (AEs) Meeting Protocol-defined Dose-limiting Toxicity (DLT) Criteria
timeFrame: From first dose of study medication through 60 days following last dose of study treatment (assessed for an average of 7 months up to a max of approximately 27 months)
measure: Number of Participants With Adverse Events (AEs) Leading to Discontinuation
timeFrame: From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
measure: Number of Participants Who Died
timeFrame: From randomization (Part 2A and 2B) or first dose (Part 1, 2C and 2D) until study closure (Up to approximately 83 months)
measure: Objective Response Rate (ORR) for Part 2 Only
timeFrame: From the start of the study treatment until disease progression, or the last response recorded, taking into account any requirement for confirmation and censoring rules regarding subsequent therapy (Up to approximately 83 months)
measure: Median Duration of Response (mDOR) for Part 2 Only
timeFrame: From the date of first dose to the date of the first objectively documented tumor progression, or death, whichever occurs first (Up to approximately 83 months)
measure: Progression-free Survival Rate (PFSR) at 24, 36, and 48 Weeks for Part 2 Only
timeFrame: At 24, 36, and 48 weeks
Secondary outcomes:
measure: Objective Response Rate (ORR) for Part1A and Part1B Only
timeFrame: From the start of the study treatment until disease progression, or the last response recorded, taking into account any requirement for confirmation and censoring rules regarding subsequent therapy (Up to approximately 83 months)
measure: Median Duration of Response (mDOR) for Part1A and Part1B Only
timeFrame: From the date of first dose to the date of the first objectively documented tumor progression, or death, whichever occurs first (Up to approximately 83 months)
measure: Progression-free Survival Rate (PFSR) at 24, 36, and 48 Weeks for Part1A and Part1B Only
timeFrame: At 24, 36, and 48 weeks
measure: Maximum Observed Serum Concentration (Cmax) for BMS-986218
timeFrame: On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
measure: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] for BMS-986218
timeFrame: On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
measure: Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] for BMS-986218
timeFrame: On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
measure: Observed Concentration at the End of a Dosing Interval (Ctau) for BMS-986218
timeFrame: On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
measure: Total Body Clearance (CLT/F) for BMS-986218
timeFrame: At Cycle 3 Day 1 (Each Cycle is of 28 Days)
measure: Average Concentration Over a Dosing Interval (AUC[TAU]/Tau) at Steady State (Css-avg) for BMS-986218
timeFrame: At Cycle 3 Day 1 (Each Cycle is of 28 Days)
measure: Ratio of an Exposure Measure at Steady State to That After the First Dose (Exposure Measure Includes Cmax) (AI_Cmax) for BMS-986218
timeFrame: At Cycle 3 Day 1 (Each Cycle is of 28 Days)
measure: Accumulation Index Ratio of AUC at Steady State to That After the First Dose (AI_AUC) for BMS-986218
timeFrame: At Cycle 3 Day 1 (Each Cycle is of 28 Days)
measure: Terminal Serum Half-life (T-HALF) for BMS-986218
timeFrame: At Cycle 3 Day 1 (Each Cycle is of 28 Days)
measure: Time of Maximum Observed Concentration (Tmax) for BMS-986218
timeFrame: On Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 (Each Cycle is of 28 Days)
measure: Trough Observed Plasma Concentration (Ctrough) for BMS-986218
timeFrame: At Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 21 Day 1 (Each Cycle is of 28 Days)
measure: Number of Participants With Anti-drug Antibodies (ADA) to BMS-986218
timeFrame: From first dose of study medication through 100 days following last dose of study treatment (assessed for an average of 8 months up to a max of approximately 28 months)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Local Institution - 0058
state: Georgia
city: Boston
country: United States
facility: Local Institution - 0025
state: Massachusetts
city: Hackensack
country: United States
facility: Local Institution - 0002
state: New Jersey
city: New Brunswick
country: United States
facility: Local Institution - 0028
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0001
state: New York
city: New York
country: United States
facility: Local Institution - 0007
state: New York
city: Monroeville
country: United States
facility: Local Institution - 0015
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0004
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Local Institution - 0033
state: South Dakota
city: Ciudad Autónoma De Buenos Aires
country: Argentina
facility: Local Institution - 0042
state: Buenos Aires
city: ABB
country: Argentina
facility: Local Institution - 0053
state: Ciudad Autónoma De Buenos Aires
city: Caba
country: Argentina
facility: Local Institution - 0057
state: Ciudad Autónoma De Buenos Aires
city: Córdoba
country: Argentina
facility: Local Institution - 0062
state: Cordoba
city: Rio Cuarto
country: Argentina
facility: Local Institution - 0060
state: Cordoba
city: Villa Siburu
country: Argentina
facility: Local Institution - 0047
state: Cordoba
city: Buenos Aires
country: Argentina
facility: Local Institution - 0059
state: Distrito Federal
city: Northmead
country: Australia
facility: Local Institution - 0026
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Local Institution - 0006
state: New South Wales
city: Murdoch
country: Australia
facility: Local Institution - 0049
state: Western Australia
city: Gent
country: Belgium
facility: Local Institution - 0039
city: Edmonton
country: Canada
facility: Local Institution - 0037
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution - 0023
state: British Columbia
city: Ottawa
country: Canada
facility: Local Institution - 0027
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0022
state: Ontario
city: Santiago
country: Chile
facility: Local Institution - 0048
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0041
state: Metropolitana
city: Vina del Mar
country: Chile
facility: Local Institution - 0052
state: Valparaiso
city: Helsinki
country: Finland
facility: Local Institution - 0045
city: Lyon Cedex 08
country: France
facility: Local Institution - 0019
city: Toulouse Cedex 9
country: France
facility: Local Institution - 0020
city: Villejuif
country: France
facility: Local Institution - 0018
city: Dresden
country: Germany
facility: Local Institution - 0009
city: Essen
country: Germany
facility: Local Institution - 0030
city: Haifa
country: Israel
facility: Local Institution - 0029
city: Ramat Gan
country: Israel
facility: Local Institution - 0008
city: Napoli
country: Italy
facility: Local Institution - 0011
city: Rozzano
country: Italy
facility: Local Institution - 0061
city: Siena
country: Italy
facility: Local Institution - 0010
city: Amsterdam
country: Netherlands
facility: Local Institution - 0038
city: Nijmegen
country: Netherlands
facility: Local Institution - 0043
city: Oslo
country: Norway
facility: Local Institution - 0040
city: Warszawa
country: Poland
facility: Local Institution - 0036
city: Cluj Napoca
country: Romania
facility: Local Institution - 0034
city: Craiova
country: Romania
facility: Local Institution - 0035
city: Barcelona
country: Spain
facility: Local Institution - 0014
city: Madrid
country: Spain
facility: Local Institution - 0056
city: Madrid
country: Spain
facility: Local Institution - 0055
city: Madrid
country: Spain
facility: Local Institution - 0013
city: Malaga
country: Spain
facility: Local Institution - 0054
city: Pamplona
country: Spain
facility: Local Institution - 0012
city: Lausanne
country: Switzerland
facility: Local Institution - 0017
city: Zuerich
country: Switzerland
facility: Local Institution - 0031
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol Myers Squibb
role: STUDY_DIRECTOR
References: