The goal of this interventional study is to determine the strength of cobolimab and dostarlimab that is most tolerated in children and young adults who have advanced solid tumors. This study also aims: (a) to check if it is safe to use cobolimab and dostarlimab combination in children and young adults, (b) to see how to manage the side effects that may occur, and (c) the effect of this treatment in participants
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Cobolimab will be administered
Dostarlimab will be administered
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Iowa City, Iowa, United States
GSK Investigational Site
Hackensack, New Jersey, United States
GSK Investigational Site
Cincinnati, Ohio, United States
GSK Investigational Site
Providence, Rhode Island, United States
GSK Investigational Site
Madison, Wisconsin, United States
GSK Investigational Site
Brno, Czechia
GSK Investigational Site
Phaha 5, Czechia
GSK Investigational Site
Copenhagen, Denmark
GSK Investigational Site
Bordeaux, France
...and 10 more locations
Part 1- Number of participants with Dose Limiting Toxicities (DLTs)
Time frame: Up to 42 days
Part 1- Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), immune-mediated adverse events (imAEs) and adverse events (AEs) leading to discontinuation occurring during the study
Time frame: Up to approximately 46 months
Part 1- Serum concentration of Cobolimab
Time frame: 1±0.5 hours (h) post-dose on Cycle 1 Day 1; 168±12 h post-dose Cycle 1Day 8; Pre-dose and 1±0.5 h post-dose on Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1(Each cycle is of 21 days)
Part 1- Serum concentration of Dostarlimab
Time frame: 1±0.5 h post start of cobolimab infusion on Cycle 1 Day 1; Pre-dose on Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1(Each cycle is of 21 days)
Part 1- Recommended Phase 2 Dose (RP2D) of Cobolimab and Dostarlimab combination
Time frame: Up to approximately 12 months
Part 2- Confirmed Objective Response Rate (ORR)
Confirmed ORR is defined as the proportion of participants who have achieved confirmed complete response (CR) or confirmed partial response (PR), evaluated using disease-specific tumor assessment criteria based on Investigator assessment
Time frame: Up to approximately 46 months
Part 2- Number of participants with TEAEs, SAEs, imAEs, TEAEs leading to death and AEs leading to discontinuation
Time frame: Up to approximately 46 months
Part 2-Number of participants with changes in laboratory parameters, vital signs and cardiac parameters
Time frame: Up to approximately 46 months
Part 1 and 2: Receptor occupancy (RO)
RO will be measured in whole blood and presented as normalized ratio \[Fluorescence Minus One (FMO) subtracted values of free T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) to total TIM-3\]
Time frame: Pre-dose Cycle 1 Day 1, 5 h post-start of cobolimab administration Cycle 1 Day 1, anytime Cycle 1 Day 8, pre-dose Cycle 2 Day 1, and pre-dose Cycle 4 Day 1 (Each cycle is of 21 days)
Part 1- Confirmed ORR
Confirmed ORR is defined as the proportion of participants who have achieved confirmed CR or confirmed PR, evaluated using disease specific tumor assessment criteria based on Investigator assessment
Time frame: Up to approximately 70 months
Part 1 and 2: Progression Free Survival (PFS)
PFS is defined as the length of time until disease progression, from the date of first dose to the earliest date of assessment of disease progression based on disease-specific tumor assessment criteria by Investigator assessment, or death by any cause, whichever occurs first
Time frame: Up to approximately 70 months
Part 1 and 2: Duration of response (DOR)
DOR is defined as the time from first documented response (CR/PR) until the time of first documentation of disease progression based on disease-specific tumor assessment criteria by Investigator assessment, or death, whichever occurs first
Time frame: Up to approximately 70 months
Part 1 and 2: Overall Survival (OS)
OS is defined as the time from the date of first dose to the date of death by any cause
Time frame: Up to approximately 70 months
Part 1 and 2: Number of participants with positive results in Anti-drug antibody (ADA) test against Cobolimab
Time frame: Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
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Part 1 and 2: Number of participants with positive results in Anti-drug antibody (ADA) test against Dostarlimab
Time frame: Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 1 and 2: Titers of ADA to Cobolimab
Time frame: Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 1 and 2: Titers of ADA to Dostarlimab
Time frame: Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 2- Serum concentration of Cobolimab
Time frame: 1±0.5 hours(h) post-dose on Cycle1Day 1;168±12h post-dose Cycle1Day8; Pre-dose & 1±0.5h post-dose on Cycle2Day1; Cycle4Day1 & Cycle6Day1[Each cycle is of 21 days];End of Treatment(EOT; EOT is within 7days of last dose), 30Day safety follow up(FUP) Visit
Part 2- Serum concentration of Dostarlimab
Time frame: 1±0.5 h post start of cobolimab infusion on Cycle 1 Day 1; Pre-dose on Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1 [Each cycle is of 21 days]; End of Treatment (EOT; EOT is within 7 days of last dose), 30-Day safety follow up (FUP) Visit