Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors

Conditions

• Neoplasms

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Dostarlimab — BIOLOGICAL
  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 Details

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.

Key Dates

Start date

Mar 7, 2016

Status verified

Jan 2026

Primary completion

May 18, 2026

Completion

Jan 25, 2027

Study Design

Enrollment

730 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Part 1: Participants receiving dostarlimab
  Part 1 will evaluate dostarlimab at ascending weight-based doses 1 mg/kg, 3 mg/kg and 10 mg/kg. Higher dose levels 15 mg/kg and/or 20 mg/kg may also be explored. Dostarlimab will be administered intravenously (IV) on Day 1 and Day 15 of each cycle; cycle length is 28 days. Cohorts will be enrolled sequentially and will initially follow a 3+3 design.
• Experimental: Part 2A: Participants receiving dostarlimab
  In Part 2A, participants will receive fixed dose of 500 mg administered Q3W or 1000 mg administered Q6W dose on Day 1 of each cycle. Cycle duration for Q3W dosing is 21 days and Q6W dosing is 42 days. Cohorts will enroll participants with advanced solid tumor using a modified 6+6 design and will follow a 6+6 design.
• Experimental: Part 2B: Cohort A1 dMMR/MSI-H endometrial cancer
  Part 2B: Cohort A1 will include participants with mismatch repair deficient microsatellite instability high (dMMR/MSI-H) endometrial cancer who have progressed on or after platinum doublet therapy. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles. Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage \>= IIIB) disease.
• Experimental: Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancer
  Part 2B: Cohort A2 will include participants with MMR-proficient/MSS endometrial cancer who have progressed on or after platinum doublet therapy. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles. Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage \>=IIIB) disease.
• Experimental: Part 2B: Cohort E NSCLC
  Part 2B: Cohort E NSCLC will include participants with non-small cell lung cancer (NSCLC) who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.
• Experimental: Part 2B: Cohort F non-endometrial dMMR/MSI-H or POLE-Mut cancers
  Participants with recurrent or advanced dMMR/MSI-H solid tumors except endometrial cancers, and gastrointestinal cancers, who have received prior systemic therapy and, who have no alternative treatment options. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.
• Experimental: Part 2B: Cohort G PROC without known BRCA
  Participants with advanced, relapsed, high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease receiving dostarlimab and who have also been previously treated with bevacizumab. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Primary Outcome Measure

Part 1: Number of participants with treatment emergent AEs (TEAEs) [ Time Frame: Up to 2 years ]

Locations (47)

Find similar trials in Birmingham, AL

Related Studies

• Collection of Tissue Specimens From Patients With Solid Tumors or Blood Disorders and Their HLA-Compatible Family Members
  Recruiting · National Heart, Lung, and Blood Institute (NHLBI) · Bethesda, Maryland
• Novel Serum Markers for Monitoring Response to Anti-Cancer Therapy
  Recruiting · Stanford University · Stanford, California
• Barrett's Esophagus Related Neoplasia (BERN) Project
  Recruiting · Midwest Biomedical Research Foundation · Kansas City, Missouri
• Collection of Tissue Samples for Cancer Research
  Recruiting · National Cancer Institute (NCI) · Sacramento, California