Clinical Trial - NCT02817633

       

A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)

Recruiting

Sponsor: Tesaro, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02817633

Protocol Info

Short Description: Phase 1 of TSR-022 in Advanced Solid Tumors
Long Description: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors
MGH Status: Open
Sponsor: Tesaro
Disease Program: Phase I

Next Steps


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Purpose

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022. The study will be conducted in 2 parts: with Part 1 consisting of dose escalation and Part 2 dose expansion. Part 1 will determine the recommended Phase 2 dose (RP2D) of TSR-022 as a single agent (Part 1a); in combination with anti-programmed cell death protein-1 (PD-1) antibody, nivolumab (Part 1b); in combination with anti-PD-1 antibody, TSR-042 (Part 1c); in combination with TSR-042 and anti-lymphocyte-activation gene 3 (LAG-3) antibody, TSR-033 (Part 1d); in combination with TSR-042 in participants not previously treated with programmed death-ligand 1 [PD-(L)1] (Part 1e) and in combination with docetaxel (Part 1f). Part 2 of the study will evaluate the antitumor activity of TSR-022, both as monotherapy and in combination with TSR-042 in participants with pre-specified tumor types.
Condition Title Intervention Phase
Neoplasms TSR-022 Nivolumab TSR-042 TSR-033 Docetaxel Phase 1
Study Type Interventional
Official Title A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)

Primary Outcome Measures

Part 1: Number of participants achieving dose limiting toxicity (DLTs) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with Serious adverse events (SAEs) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with treatment-emergent adverse event (TEAE) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with TEAEs leading to death [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with AEs leading to discontinuation [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with immune-related adverse events (irAEs) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal hematology parameters [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal clinical chemistry parameters [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal thyroid function [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal urine parameters [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal vital signs [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal electrocardiogram (ECG) findings [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with abnormal physical examination [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status scores [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Number of participants receiving concomitant medications [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]


Secondary Outcome Measures

Number of participants with anti-TSR-022 antibodies [Time Frame: Up to 2 years] [Designated as safety issue: ]

Number of participants with anti-TSR-042 antibodies [Time Frame: Up to 2 years] [Designated as safety issue: ]

Number of participants with anti-TSR-033 antibodies [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: ORR by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: ORR by immune-related RECIST (irRECIST) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Duration of response (DOR) by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Duration of response (DOR) by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Disease control rate (DCR) by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Disease control rate (DCR) by irRECIST [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Disease control rate (DCR) by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Disease control rate (DCR) by irRECIST [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Progression-free survival (PFS) by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Progression-free survival (PFS) by irRECIST [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Progression-free survival (PFS) by RECIST version 1.1 [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Progression-free survival (PFS) by irRECIST [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1: Overall survival (OS) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 2: Overall survival (OS) [Time Frame: Up to 2 years] [Designated as safety issue: ]

Part 1a: Maximum plasma concentration (Cmax) of TSR-022 when administered as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose.] [Designated as safety issue: ]

Part 1b: Cmax of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: Cmax of TSR-022 when administered in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: Cmax of TSR-022 when administered in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: Cmax of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: Cmax of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: Cmax of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Minimum plasma concentration (Cmin) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: Cmin of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: Cmin of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose.] [Designated as safety issue: ]

Part 1d: Cmin of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: Cmin of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy. [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: Cmin of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: Cmin of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Area under the concentration × time curve from time 0 to infinity AUC (0-inf) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: AUC (0-inf) of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: AUC (0-inf) of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: AUC (0-inf) of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: AUC (0-inf) of in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: AUC (0-inf) of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: AUC (0-inf) of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Area under the concentration × time curve at steady state (AUCss) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: AUCss of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: AUCss of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: AUCss of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: AUCss of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: AUCss of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: AUCss of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Maximum plasma concentration at steady state (Cmax,ss) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: Cmax,ss of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: Cmax,ss of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: Cmax,ss of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e : Cmax,ss of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f : Cmax,ss of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: Cmax,ss of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Minimum plasma concentration at steady state (Cmin,ss) of TSR-022 022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: Cmin,ss of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: Cmin,ss of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: Cmin,ss of of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: Cmin,ss of of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: Cmin,ss of of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: Cmin,ss of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Area under the concentration time curve from time 0 to last assessment (AUC 0-last) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: AUC 0-last of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: AUC 0-last of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: AUC 0-last of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: AUC 0-last of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: AUC 0-last of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: AUC 0-last of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Clearance (CL) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: CL of TSR-022 in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: CL of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: CL of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e : CL of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: CL of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: CL of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Volume of distribution (Vz) of TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: Vz of TSR-022 and in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: Vz of TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: Vz of TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e : Vz of TSR-022 in combination with TSR-042 in participants not previously treated with anti-PD-(L)1 therapy [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: Vz of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: Vz of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1a: Terminal half life (t½) TSR-022 as monotherapy [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1b: t½ of TSR-022 and in combination with nivolumab [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1c: t½ TSR-022 in combination with TSR-042 [Time Frame: Pre-dose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336 hours post dose] [Designated as safety issue: ]

Part 1d: t½ TSR-022 in combination with TSR-042 and TSR-033 [Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2.5, 3, 24, 48, 96, 168,336 hours post dose] [Designated as safety issue: ]

Part 1e: t½ TSR-022 in combination with TSR-042 in participants not previously treated with PD-(L)1 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 1f: t½ of TSR-022 in combination with TSR-042 and docetaxel [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Part 2: t½ of TSR-022 [Time Frame: Predose, 0.25, 0.5 hour post dose] [Designated as safety issue: ]

Estimated Enrollment: 369
Study Start Date: July 2016
Estimated Study Completion Date: October 2023
Estimated Primary Completion Date: October 2021
Arms Assigned Interventions

Experimental:Part 1a: TSR-022 monotherapy

Part 1a (monotherapy dose escalation) will evaluate TSR-022 at ascending weight-based doses. TSR-022 will be administered intravenously (IV).
Drug:TSR-022
TSR-022 is a humanized immunoglobulin 4 (IgG4) mAb.

Experimental:Part 1b: TSR-022 in combination with nivolumab

Participants in Part 1b will receive nivolumab at the standard dose in combination with ascending doses of TSR-022. The starting dose of TSR-022 will be the Part 1a dose at which less than or equal to (<=)1 of 6 participants experienced dose-limiting toxicity (DLTs).
Drug:Nivolumab
Nivolumab is a humanized IgG4 monoclonal antibody.

Experimental:Part 1c: TSR-022 in combination with TSR-042

Participants in Part 1c will receive escalating doses of TSR-022 in combination with TSR-042.
Drug:TSR-042
TSR-042 is a humanized IgG4 monoclonal.

Experimental:Part 1d: TSR-022 in combination with TSR-042 and TSR-033

Part 1d will initially evaluate TSR-022 and TSR-033, at ascending doses in combination with TSR-042 at a constant dose. At each dose escalation step, only 1 drug will be escalated, either TSR-022 or TSR-033.
Drug:TSR-033
TSR-033 is a humanized IgG4 monoclonal antibody.

Experimental:Part 1e: TSR-022 in combination with TSR-042

Part 1e will evaluate TSR-022 in combination with TSR-042 in participants with select cancer types who have not received prior treatment with anti-PD-L1.

Experimental:Part 1f: TSR-022 in combination with TSR-042 and Docetaxel

Part 1f will evaluate the triple combination therapy of TSR-022, TSR-042 , and docetaxel, Q3W, for safety. The starting dose of docetaxel will be 75 mg/m^2.
Drug:Docetaxel
Docetaxel is a commercially available chemotherapeutic agent.

Experimental:Part 2: Cohort A (Melanoma) (TSR-022 as monotherapy)

Participants with advanced or metastatic melanoma will be enrolled in Cohort A and will receive treatment with TSR-022 at RP2D as monotherapy.

Experimental:Part 2: Cohort A (Melanoma) (TSR-022 with TSR-042)

Participants with advanced or metastatic melanoma will be enrolled in Cohort A and will receive treatment with TSR-022 at RP2D in combination with TSR-042.

Experimental:Part2:CohortB Non-small cell lung cancer (TSR-022-monotherapy)

Participants with advanced or metastatic Non-small cell lung cancer (NSCLC) will be enrolled in Cohort B and will receive treatment with TSR-022 at RP2D as monotherapy.

Experimental:Part2:CohortB Non-small cell lung cancer(TSR-022 with TSR-042)

Participants with advanced or metastatic NSCLC will be enrolled in Cohort B and will receive treatment with TSR-022 at RP2D in combination with TSR-042.

Experimental:Part2:CohortC Colorectal cancer (TSR-022 as monotherapy)

Participants with advanced/metastatic Colorectal cancer (CRC) will be enrolled in this arm and will receive treatment with TSR-022 at RP2D as monotherapy.

Experimental:Part2:CohortC Colorectal cancer (TSR-022 with TSR-042)

Participants with advanced/metastatic CRC will be enrolled in Cohort C and will receive treatment with TSR-022 at RP2D in combination with TSR-042.

Experimental:Part 2: Cohort D (TIM-3 selected NSCLC)

Participants with advanced or metastatic NSCLC having a positive TIM-3 expression will be enrolled in Cohort D. Participants will be administered TSR-022 at RP2D in combination with TSR-042.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria

  • • Participant is at least 18 years of age.
  • • Female participants of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication or be of non-childbearing potential.
  • • Participant has adequate organ function.

Inclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C:

  • • Participant with advanced or metastatic solid tumor who meets the requirements for the part of the study/cohort he/she will participate in, as follows:
  • • Part 1: Participant with advanced or metastatic solid tumor and has disease progression after treatment with available therapies that are known to confer clinical benefit or who is intolerant to treatment (except for Part 1e, where special interest tumor types will be specified by the Sponsor).
  • • Part 1e:
  • • Advanced or metastatic melanoma participants who have not been previously treated with anti-PD-1, anti-PD-L1, or anti cytotoxic T lymphocyte-associated protein-(CTLA-4) therapies. Participant may be treatment naïve.
  • • Advanced or metastatic NSCLC participants who have not received anti-PD-1 or anti-PD-L1 therapies and have received <=2 prior lines of treatment.
  • • Part 2: Histologically proven advanced (unresectable) or metastatic solid tumor that is measurable by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST version 1.1 criteria and meets 1 of the following disease types:
  • • Cohort A (melanoma) - Participants with advanced or metastatic melanoma who have progressed following treatment with an anti-PD-1 or anti-PD-L1 antibody.
  • • Cohort B (NSCLC) - Participants with advanced or metastatic NSCLC who have progressed following:
  • • Treatment with an anti-PD-1 or anti-PD-L1 antibody.
  • • Cohort C (CRC) - Participants with advanced/metastatic CRC who have progressed following standard treatment which must include fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated. Participants should have received no more than 3 prior lines of therapy (including adjuvant therapy).
  • • Biopsies
  • • Part 1: Participants must have archival tumor tissue available that is formalin-fixed and paraffin-embedded. Tumor tissue must be requested from off-site locations and confirmed available prior to dosing.
  • • For participants in Part 1 who do not have archival tissue, a new biopsy must be performed to obtain tumor tissue.
  • • Part 2 Cohorts A, B, and C: All participants enrolled in Part 2 Cohorts A to C are required to have fresh tumor tissue biopsy prior to dosing. Archival tissue should also be provided (if available) to enable a longitudinal analysis of tumor biomarkers.
  • • If a participants has had a biopsy prior to entering the 21-day screening period and within approximately 12 weeks of study treatment, that biopsy may be accepted as the Baseline fresh biopsy.
  • • All participants are also required to have lesions amenable to biopsy and to agree to tumor biopsies prior to the initiation of treatment (as noted above) approximately 4 to 6 weeks after initiating treatment, and, if possible, upon treatment discontinuation (for participant with PD).
  • • Inclusion Criteria for Participants in Part 2 Cohort D
  • • Participants with advanced or metastatic NSCLC that is measurable by CT or MRI per RECIST version 1.1 criteria and meet the following criteria:
  • • NSCLC histology includes squamous or non-squamous cell carcinoma.
  • • Participants have received no more than 2 prior lines of therapy, which must include a platinum-based chemotherapy (eg, cisplatin, carboplatin) and an anti-PD-(L)1 antibody.
  • • Participants must have documented radiographic progression by RECIST version 1.1 criteria on prior anti-PD-1 or anti-PD-L1 therapy.
  • • Biopsies
  • • If a participant has had a biopsy prior to entering the 35-day screening period and within approximately 12 weeks of study treatment, that biopsy may be accepted as the Baseline fresh biopsy.

Exclusion Criteria

  • • History of Grade >=3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
  • • Participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • • Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the Medical Monitor.
  • • Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy.
  • • Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment.
  • • Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • • Participant has a known history of human immunodeficiency virus (HIV) infection or HIV 1/2 antibodies.
  • • Participant has known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected).
  • • Participant has an active autoimmune disease that has required systemic treatment (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs).
  • • Participant has a history of pneumonitis.
  • • Participant has not recovered (ie, to Grade <=1 or to Baseline) from radiation- and chemotherapy-induced AEs, has received transfusion of blood products (including platelets or red blood cells), or has received administration of colony-stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.
  • • Participant is currently participating and receiving study therapy or has participated in a study of an investigational agent and received investigational therapy or used an investigational device within 4 weeks prior to the first dose of study drug.
  • • Participant has received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter.
  • • Participant has not recovered adequately (Grade <=1) from AEs and/or complications from any major surgery prior to starting therapy.
  • • Participant has received a vaccine within 7 days of planned start of study therapy.
  • • Participant has a known hypersensitivity to TSR-022 components or excipients, or, if applicable, nivolumab, TSR-042, or TSR-033 components or excipients.

Exclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C

  • • Participant received prior therapy as defined below:
  • • Part 1a: Anti-CTLA-4, anti-PD-1, anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent within 3 weeks (that is, 21 days) prior to initiation of study treatment.
  • • Part 1b, Part 1c, Part 1d, and Part1f: Anti-CTLA-4 within 3 weeks (that is, 21 days) prior to initiation of study treatment and/or prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIM-3, or anti-LAG-3, or docetaxel agent that resulted in permanent discontinuation due to an AE.
  • • Part 1e: Prior treatment with with an anti-PD-(L)1, anti-LAG-3 or anti-TIM-3.
  • • NSCLC participants with known EGFR mutations, ALK translocations, or ROS1 mutations.
  • • Participants with uveal melanoma.
  • • Part 1f: History of severe hypersensitivity reaction to docetaxel, paclitaxel, or other drugs formulated with polysorbate 80.
  • • Part 2 Cohorts A, B, and C combination arms (TSR-022 + TSR-042):
  • • Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE.
  • • Prior treatment with an anti-LAG-3 or anti-TIM-3.

Exclusion Criteria for Participants in Part 2 Cohort D

  • • A participant with negative (as determined by Central Testing Lab) or unevaluable TIM-3 expression from tissue obtained prior to study entry will not be eligible for the study.
  • • Participant has received prior therapy as defined below:
  • • Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE.
  • • Prior treatment with an anti-LAG-3 or anti-TIM-3.
  • • Radiologic or clinical progression <= 8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody.
  • • Participants with known EGFR mutation, ALK translocation, or ROS1 mutation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02817633

Locations

  • United States, Arizona
    • GSK Investigational Site Goodyear, Arizona, United States, 85338
    • GSK Investigational Site Phoenix, Arizona, United States, 85054
    • GSK Investigational Site Scottsdale, Arizona, United States, 85258
    • GSK Investigational Site Tucson, Arizona, United States, 85704
    • GSK Investigational Site Tucson, Arizona, United States, 85711
  • United States, California
    • GSK Investigational Site Encinitas, California, United States, 92024
    • GSK Investigational Site Fountain Valley, California, United States, 92708
    • GSK Investigational Site Los Angeles, California, United States, 90024
    • GSK Investigational Site Los Angeles, California, United States, 90025
    • GSK Investigational Site San Marcos, California, United States, 92069
    • GSK Investigational Site Whittier, California, United States, 90606
  • United States, Colorado
    • GSK Investigational Site Aurora, Colorado, United States, 80012
    • GSK Investigational Site Aurora, Colorado, United States, 80045
    • GSK Investigational Site Denver, Colorado, United States, 80218
  • United States, Connecticut
    • GSK Investigational Site New Haven, Connecticut, United States, 06511
  • United States, District of Columbia
    • GSK Investigational Site Washington, District of Columbia, United States, 20007
  • United States, Florida
    • GSK Investigational Site Jacksonville, Florida, United States, 32224
    • GSK Investigational Site Miami Beach, Florida, United States, 33140
    • GSK Investigational Site Sarasota, Florida, United States, 34232
    • GSK Investigational Site Tampa, Florida, United States, 33612
  • United States, Georgia
    • GSK Investigational Site Atlanta, Georgia, United States, 30322
    • GSK Investigational Site Augusta, Georgia, United States, 30912
  • United States, Illinois
    • GSK Investigational Site Arlington Heights, Illinois, United States, 60005
    • GSK Investigational Site Chicago, Illinois, United States, 60604-1104
    • GSK Investigational Site Chicago, Illinois, United States, 60637
    • GSK Investigational Site Niles, Illinois, United States, 60714
  • United States, Iowa
    • GSK Investigational Site Iowa City, Iowa, United States, 52242-1009
  • United States, Kansas
    • GSK Investigational Site Wichita, Kansas, United States, 67214
  • United States, Kentucky
    • GSK Investigational Site Louisville, Kentucky, United States, 40202
    • GSK Investigational Site Pikeville, Kentucky, United States, 41501
  • United States, Maryland
    • GSK Investigational Site Rockville, Maryland, United States, 20850
  • United States, Massachusetts
    • GSK Investigational Site Boston, Massachusetts, United States, 02114
  • United States, Michigan
    • GSK Investigational Site Detroit, Michigan, United States, 48202
  • United States, Minnesota
    • GSK Investigational Site Rochester, Minnesota, United States, 55905
  • United States, New Jersey
    • GSK Investigational Site Hackensack, New Jersey, United States, 07601
  • United States, New Mexico
    • GSK Investigational Site Farmington, New Mexico, United States, 87401
  • United States, New York
    • GSK Investigational Site Bronx, New York, United States, 10461
    • GSK Investigational Site New York, New York, United States, 10016-4744
  • United States, Ohio
    • GSK Investigational Site Cincinnati, Ohio, United States, 45242
    • GSK Investigational Site Cleveland, Ohio, United States, 44106
  • United States, Oregon
    • GSK Investigational Site Eugene, Oregon, United States, 97401
    • GSK Investigational Site Portland, Oregon, United States, 97213-2982
  • United States, Pennsylvania
    • GSK Investigational Site Bethlehem, Pennsylvania, United States, 18015
    • GSK Investigational Site Pittsburgh, Pennsylvania, United States, 15232
  • United States, South Carolina
    • GSK Investigational Site Charleston, South Carolina, United States, 29425
    • GSK Investigational Site Greenville, South Carolina, United States, 29605
  • United States, Tennessee
    • GSK Investigational Site Nashville, Tennessee, United States, 37203
  • United States, Texas
    • GSK Investigational Site Austin, Texas, United States, 78705
    • GSK Investigational Site Dallas, Texas, United States, 75246
    • GSK Investigational Site Fort Worth, Texas, United States, 76104
    • GSK Investigational Site Houston, Texas, United States, 77030
    • GSK Investigational Site Houston, Texas, United States, 77030
    • GSK Investigational Site Longview, Texas, United States, 75601
    • GSK Investigational Site McAllen, Texas, United States, 78503-1298
    • GSK Investigational Site San Antonio, Texas, United States, 78229
    • GSK Investigational Site Temple, Texas, United States, 76508
    • GSK Investigational Site Tyler, Texas, United States, 75702
    • GSK Investigational Site Weslaco, Texas, United States, 78596
  • United States, Virginia
    • GSK Investigational Site Fairfax, Virginia, United States, 22031
  • United States, Washington
    • GSK Investigational Site Kennewick, Washington, United States, 99336
    • GSK Investigational Site Puyallup, Washington, United States, 98373
    • GSK Investigational Site Tacoma, Washington, United States, 98405
  • United States, Wisconsin
    • GSK Investigational Site Madison, Wisconsin, United States, 53792
  • Spain, Navarra
    • GSK Investigational Site Madrid, Navarra, Spain, 28027
  • Spain,
    • GSK Investigational Site Girona, , Spain, 17007
    • GSK Investigational Site Madrid, , Spain, 28040
    • GSK Investigational Site Madrid, , Spain, 28041
    • GSK Investigational Site Madrid, , Spain, 28050
    • GSK Investigational Site Málaga, , Spain, 29010
    • GSK Investigational Site Pamplona, , Spain, 31008
    • GSK Investigational Site Valencia, , Spain, 46010

Sponsors and Collaborators

Tesaro, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02817633
Other Study ID Numbers: 4020-01-001
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Tesaro, Inc.:

Antibodies

TSR-022

Cobolimab

Advanced solid tumors

Metastatic solid tumors

Immunotherapy

PD-1

Anti-PD-1

Colorectal cancer

Non-small cell lung cancer

Melanoma

Anti-LAG-3

TSR-033

TSR-042

Dostarlimab

Additional relevant MeSH terms:

Docetaxel

Nivolumab

Next Steps


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ClinicalTrials.gov processed this data on February 25, 2021