Study of TSR-033 With an Anti-programmed Cell Death-1 Receptor (PD-1) in Participants With Advanced Solid Tumors

Part of paid clinical trials in Los Angeles, California.

Sponsor
Tesaro, Inc.
Study ID
NCT03250832
Phase
PHASE1
Status
Completed

Conditions

  • Neoplasms

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • TSR-033 — DRUG
    TSR-033 is a humanized monoclonal antibody immunoglobulin (Ig) G4.
  • Dostarlimab — DRUG
    Dostarlimab (previously referred to as TSR-042) is an IgG4 antibody.
  • mFOLFOX6 — DRUG
    mFOLFOX6 is combination of folinic acid (FOL)/leucovorin, 5-fluorouracil and oxaliplatin (OX) which acts as systemic cytotoxic agent.
  • FOLFIRI — DRUG
    FOLFIRI is combination of folinic acid (FOL)/leucovorin, 5-fluorouracil and irinotecan (IRI) which acts as systemic cytotoxic agent.
  • Bevacizumab — DRUG
    Bevacizumab is a humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor (VEGF)-A to inhibit angiogenesis.

Study Details

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-lymphocyte activation gene-3 (LAG-3) antibody TSR-033 alone, in combination with the anti-PD-1 antibody dostarlimab, and in combination with dostarlimab, modified folinic acid (FOL)/leucovorin, 5-fluorouracil and oxaliplatin (OX) (mFOLFOX6) or FOL/leucovorin, 5-fluorouracil and irinotecan (IRI) (FOLFIRI), and bevacizumab in participants with advanced solid tumors in a broad range of solid tumors. Participants with disease types selected for evaluation in this study are expected to derive clinical benefit with addition of an anti-PD-1. The study will be conducted in two parts with Part 1 consisting of dose escalation to determine the recommended phase 2 dose (RP2D) of TSR-033 as a single agent (Part 1a) and in combination with dostarlimab (Part 1c). RP2D decisions will be based on the occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), as well as pharmacodynamics (PDy) data. Part 2A of the study will investigate the anti-tumor activity of TSR-033 and dostarlimab in combination in participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC). Part 2B of the study will investigate the safety and anti-tumor activity of TSR-033 and dostarlimab in combination with chemotherapy (Cohort B1: mFOLFOX6 and Cohort B2: FOLFIRI) and bevacizumab in participants with advanced or metastatic MSS-CRC.

Key Dates

First listed
Aug 16, 2017
Start date
Aug 8, 2017
Status verified
Mar 2024
Primary completion
Jun 2, 2022
Completion
Feb 13, 2023

Study Design

Enrollment
111 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1a: TSR-033 monotherapy dose escalation
    Part 1a will evaluate TSR-033 at ascending doses (20 milligrams \[mg\], 80 mg and 240 mg) every 2 weeks. Cohorts will be enrolled sequentially and will initially follow a 3+3 design at a starting dose of 20 mg.
  • Experimental: Part 1b: TSR-033 monotherapy PK/PDy characterization
    Part 1b will evaluate the PK profile and assess PDy data from blood and tumor tissue samples following TSR-033 treatment. The participants will begin treatment with TSR-033 on Day 1 followed by 28 days observation for collection of blood sampling for PK/PDy. Participants will receive their second dose of TSR-033 on Day 29 and every 14 days thereafter.
  • Experimental: Part 1c: TSR-033+dostarlimab combination dose escalation
    Participants will be administered ascending doses of TSR-033 in combination with dostarlimab 500 mg every 3 weeks. Planned dose levels of TSR-033 include 80 and 240 mg.
  • Experimental: Part 2 Cohort A: TSR-033+dostarlimab combination
    Part 2 Cohort A will evaluate the preliminary activity of TSR-033 in combination with dostarlimab in anti-PD-1 naive participants with third and fourth line MSS-CRC. TSR-033 will be administered every 2 weeks and dostarlimab every 6 weeks.
  • Experimental: Part 2 Cohort B1: TSR-033+dostarlimab with mFOLFOX6
    Part 2 Cohort B1 will evaluate the preliminary activity of TSR-033 administered every 2 weeks (Q2W) in combination with dostarlimab administered every 6 weeks (Q6W) along with mFOLFOX6 and bevacizumab (standard of care \[SOC\]) in anti-PD-1 naive second line MSS-CRC participants who have progressed on frontline treatment with FOLFIRI, with or without biologics.
  • Experimental: Part 2 Cohort B2: TSR-033+dostarlimab with FOLFIRI
    Part 2 Cohort B2 will evaluate the preliminary activity of TSR-033 in combination with FOLFIRI and bevacizumab (SOC) in anti-PD-1 naive second line MSS-CRC participants who have progressed on frontline treatment with FOLFOX, with or without biologics.

Primary Outcome Measure

Part 1A: Number of Participants Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]

Locations (11)

FacilityCityStateZIPSite coordinators
GSK Investigational SiteLos AngelesCalifornia90095-
GSK Investigational SiteWhittierCalifornia90603-
GSK Investigational SiteSarasotaFlorida34232-
GSK Investigational SiteTampaFlorida33612-
GSK Investigational SiteBostonMassachusetts02115-
GSK Investigational SiteClevelandOhio44106-
GSK Investigational SiteOklahoma CityOklahoma73104-
GSK Investigational SitePittsburghPennsylvania15232-
GSK Investigational SiteGreenvilleSouth Carolina29605-
GSK Investigational SiteHoustonTexas77030-
GSK Investigational SiteSan AntonioTexas78229-

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