Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors
Condition(s) studied
Investigational drug(s) / intervention(s)
Dostarlimab: Dostarlimab (160 mg, 20 mg/mL; or 500 mg, 50 mg/mL) is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2). Dostarlimab will be administered via a 30 minute IV infusion on Day 1 and Day 15 of each cycle in Part 1. For additional patients enrolled specifically to better characterize the PK/PDy profile in Part 1, dostarlimab administration during Cycle 1 will only occur on Day 1 with the second dose administered on Cycle 2/Day 1 and Q2W thereafter. For Part 2A and 2B, dostarlimab will be administered on Day 1 of each treatment cycle. Cycle duration for Q3W dosing is 21 days and Q6W dosing is 42 days.
Study summary
This is a multi-center, open-label, first-in-human Phase 1 study evaluating the anti-programmed death receptor 1 (anti-PD-1) antibody dostarlimab (also known as TSR-042) n participants with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts with Part 1 consisting of safety evaluation, pharmacokinetics (PK), and pharmacodynamics (PDy) of escalating doses of dostarlimab. Dose escalation will be based on ascending weight-based dose levels (DLs) of dostarlimab and will continue until the maximum tolerated dose (MTD) is reached or may be stopped at any dose level up to the highest dose of 20 milligrams per kilograms (mg/kg) based on emerging safety and PK/PDy data. Part 2 will be conducted in two subparts, Part 2A (fixed-dose safety evaluation cohorts) and Part 2B (expansion cohorts). Part 2A of the study will evaluate the safety and tolerability of dostarlimab at fixed doses of 500 mg administered every 3 weeks (Q3W) and 1000 mg administered every 6 weeks (Q6W). Part 2B of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.
Eligibility
Primary outcome measure(s)
- Part 1: Number of participants with treatment emergent AEs (TEAEs) — Up to 2 years
An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. - Part 1: Number of participants with immune mediated AEs of interest — Up to 2 years
Participants with immune related AEs of interest will be assessed. - Part 1: Number of participants with abnormal hematology parameters — Up to 2 years
Blood samples will be collected to assess the following hematology parameters: hemoglobin, Mean corpuscular (MCV), white blood cell count (WBC count), platelets, mean platelet volume, differential WBC count and coagulation factors including International normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT). - Part 1: Number of participants with abnormal clinical chemistry parameters — Up to 2 years
Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin. - Part 1, Part 2A, and Part 2B: Number of participants with a change from baseline in urinalysis parameters — Up to 2 years
Number of participants will be assessed. - Part 1, Part 2A, and Part 2B: Number of participants with a change from baseline in vital signs — Up to 2 years
Number of participants will be assessed. - Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters — Up to 2 years
Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded. - Part 1: Number of participants receiving concomitant medications — Up to 2 years
Concomitant medications will be recorded. - Part 2A: Number of participants with TEAEs — Up to 2 years
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first dose of study treatment. - Part 2A: Number of participants with immune mediated AEs of interest — Up to 2 years
Participants with immune related AEs of interest will be assessed. - Part 2A: Number of participants with abnormal hematology parameters — Up to 2 years
Blood samples will be collected to assess the following hematology parameters: hemoglobin, MCV, white WBC count, platelets, mean platelet volume, differential WBC count and coagulation factors including INR, aPTT and PT. - Part 2A: Number of participants with abnormal clinical chemistry parameters — Up to 2 years
Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, AST, ALT, and albumin. - Part 2A: Number of participants with abnormal ECG — Up to 2 years
Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded. - Part 2A: Number of participants receiving concomitant medications — Up to 2 years
Concomitant medications will be recorded. - Part 2B: Number of participants with TEAEs — Up to 2 years
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first dose of study treatment. - Part 2B: Number of participants with immune related AEs of interest — Up to 2 years
Participants with immune related AEs of interest will be assessed. - Part 2B: Number of participants with abnormal hematology parameters — Up to 2 years
Blood samples will be collected to assess the following hematology parameters: hemoglobin, MCV, white WBC count, platelets, mean platelet volume, differential WBC count and coagulation factors including INR, aPTT and PT. - Part 2B: Number of participants with abnormal clinical chemistry parameters — Up to 2 years
Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, AST, ALT, and albumin. - Part 2B: Number of participants with abnormal ECG parameters — Up to 2 years
Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded. - Part 2B: Number of participants receiving concomitant medications — Up to 2 years
Concomitant medications will be recorded. - Part 2B: Cohort A1 Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 — Up to 2 years
ORR is defined as the proportion of participants achieving complete response (CR) or partial response (PR) as evaluated by independent blinded central review using RECIST version 1.1. - Part 2B: Cohort F ORR by RECIST version 1.1 — Up to 2 years
ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1. - Part 2B: Cohort A2 ORR by RECIST version 1.1 — Up to 2 years
ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1. - Part 2B: Cohort G ORR by RECIST version 1.1 — Up to 2 years
ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1. - Part 2B: Cohort E ORR by immune related Response Evaluation Criteria in Solid Tumors per irRECIST — Up to 2 years
ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per irRECIST will be evaluated. - Part 2B: Cohort A1 Duration of response (DOR) — Up to 2 years
DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of progressive disease (PD) evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause. - Part 2B: Cohort F Duration of response (DOR) — Up to 2 years
DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause. - Part 2B: Cohort A2 Duration of response (DOR) — Up to 2 years
DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.
Trial sites (128)
| Facility | City | Region | Status |
|---|---|---|---|
| GSK Investigational Site | Birmingham | Alabama | |
| GSK Investigational Site | Goodyear | Arizona | |
| GSK Investigational Site | Scottsdale | Arizona | |
| GSK Investigational Site | Fayetteville | Arkansas | |
| GSK Investigational Site | Encinitas | California | |
| GSK Investigational Site | La Jolla | California | |
| GSK Investigational Site | Los Angeles | California | |
| GSK Investigational Site | Newport Beach | California | |
| GSK Investigational Site | San Francisco | California | |
| GSK Investigational Site | San Marcos | California | |
| GSK Investigational Site | Santa Monica | California | |
| GSK Investigational Site | Washington D.C. | District of Columbia | |
| GSK Investigational Site | Miami | Florida | |
| GSK Investigational Site | Tampa | Florida | |
| GSK Investigational Site | Augusta | Georgia | |
| GSK Investigational Site | Chicago | Illinois | |
| GSK Investigational Site | Fairway | Kansas | |
| GSK Investigational Site | Scarborough | Maine | |
| GSK Investigational Site | Baltimore | Maryland | |
| GSK Investigational Site | Boston | Massachusetts | |
| GSK Investigational Site | Boston | Massachusetts | |
| GSK Investigational Site | Detroit | Michigan | |
| GSK Investigational Site | Kansas City | Missouri | |
| GSK Investigational Site | Farmington | New Mexico | |
| GSK Investigational Site | Albany | New York | |
| GSK Investigational Site | Brooklyn | New York | |
| GSK Investigational Site | Jamaica | New York | |
| GSK Investigational Site | New York | New York | |
| GSK Investigational Site | Charlotte | North Carolina | |
| GSK Investigational Site | Cleveland | Ohio | |
| GSK Investigational Site | Columbus | Ohio | |
| GSK Investigational Site | Hilliard | Ohio | |
| GSK Investigational Site | Hilliard | Ohio | |
| GSK Investigational Site | Oklahoma City | Oklahoma | |
| GSK Investigational Site | Philadelphia | Pennsylvania | |
| GSK Investigational Site | Philadelphia | Pennsylvania | |
| GSK Investigational Site | Providence | Rhode Island | |
| GSK Investigational Site | Dallas | Texas | |
| GSK Investigational Site | Dallas | Texas | |
| GSK Investigational Site | San Antonio | Texas |
+ 88 more sites — see the full list on the official registry below.
Other trials for the same condition
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT02715284 on ClinicalTrials.gov ↗ ← All trials in Mexico