Clinical trial NCT03251924: A Dose Escalation and Combination Immunotherapy Study to Evaluate BMS-986226 Alone or in Combination With Nivolumab or Ipilimumab in Patients With Advanced Solid Tumors
Official title: A Phase 1/2 Dose Escalation and Combination Cohort Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Efficacy of BMS-986226 Alone or in Combination With Nivolumab or Ipilimumab in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Cancer
Tumors
Neoplasm
Malignancy
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-08-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate BMS-986226 administered alone or in combination with nivolumab or ipilimumab.


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

Inclusion Criteria:

* Advanced solid tumors
* Histological or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or PCWG3 (prostate only).
* At least 1 lesion accessible for biopsy in addition to the target lesion
* Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2

Exclusion Criteria:

* Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded (controlled brain metastases will be allowed to enroll)
* Participants with carcinomatous meningitis
* Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
* Active, known, or suspected autoimmune disease
* Uncontrolled or significant cardiovascular disease
* Participants with known allergies to egg products, neomycin and tetanus toxoid.
* Prior adverse reaction to tetanus toxoid- containing vaccines.

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: The Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose up to 100 days post last dose, up to approximately 31 months
measure: The Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: From first dose up to 100 days post last dose, up to approximately 31 months
measure: The Number of Participants Experiencing Adverse Events (AEs) Meeting Dose Limiting Toxicity (DLT) Criteria
timeFrame: From first dose up to 100 days post last dose, up to approximately 31 months
measure: The Number of Participants Experiencing Adverse Events Leading to Discontinuation
timeFrame: From first dose up to 100 days post last dose, up to approximately 31 months
measure: The Number of Participants Experiencing Adverse Events Resulting in Death
timeFrame: From first dose up to 100 days post last dose, up to approximately 31 months
measure: The Number of Participants Experiencing Clinical Laboratory Abnormalities
timeFrame: From first dose up to 30 days post last dose (approximately 28 months)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose up to documented disease progression, up to 48 months
measure: Median Duration of Response (DOR)
timeFrame: From first dose up to the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 24 months)
measure: Progression Free Survival (PFS) Rate at 24 Weeks
timeFrame: At 24 weeks
measure: Number of Participants With Anti-Drug Antibodies (ADA) for BMS-986226
timeFrame: Predose on cycles 1-6, post dose on C1D15, and 30, 60, and 100 days post last dose (up to approximately 31 months)
measure: Changes From Baseline in Cell Surface ICOS Expression on T Cells
timeFrame: From baseline up to pre-dose and 4 hours post dose on C1D1 and pre-dose and 4 hours post dose on C2D1 (approximately 31 months)
measure: Changes From Baseline in ICOS Ligand+ B Cells
timeFrame: From baseline up to pre-dose and 4 hours post dose on C1D1, 72 hours post dose on C1D4, and pre-dose on C2D1 (approximately 31 months)
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Effective Elimination Half-Life (T-HALFeff)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C2D1 and C3D1 (approximately 31 months)
measure: Trough Observed Serum Concentrations (Ctrough)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. Pre-dose on C5D1 and C6D1. Pre-dose and 0.5 hours post dose on C7D1. (approximately 31 months)
measure: Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Area Under Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC (0-T)]
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Area Under the Concentration-Time Curve in 1 Dosing Interval [AUC (TAU)]
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Total Body Clearance (CLT)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Average Concentration Over a Dosing Interval (Css-avg)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Accumulation Index - Area Under Curve (AI-AUC)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
measure: Accumulation Index - Cmax (AI-Cmax)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. (Approximately 31 months)
measure: Accumulation Index - Concentrations at the End of Dosing Interval (AI-CTAU)
timeFrame: Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. (Approximately 31 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Local Institution - 0005
state: Massachusetts
city: Saint Louis
country: United States
facility: Local Institution - 0012
state: Missouri
city: Hackensack
country: United States
facility: Local Institution - 0002
state: New Jersey
city: Philadelphia
country: United States
facility: Local Institution - 0001
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution - 0004
state: Tennessee
city: Edmonton
country: Canada
facility: Local Institution - 0014
state: Alberta
city: Hamilton
country: Canada
facility: Local Institution - 0006
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0003
state: Ontario
city: Madrid
country: Spain
facility: Local Institution - 0007
city: Madrid
country: Spain
facility: Local Institution - 0008
city: Chur
country: Switzerland
facility: Local Institution - 0009
city: Lausanne
country: Switzerland
facility: Local Institution - 0010
city: Zuerich
country: Switzerland
facility: Local Institution - 0011
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: