Neoadjuvant PD-1 Inhibitor Dostarlimab (TSR-042) vs. Combination of Tim-3 Inhibitor Cobolimab (TSR-022) and PD-1 Inhibitor Dostarlimab (TSR-042) in Melanoma

NCT04139902 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-047
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to test the effects of anti-PI-1 inhibitor (TSR-042) or anti-PD-1/anti-TIM-3 combination (TSR-042 / TSR-022) in patients with operable melanoma.

Conditions

Melanoma Stage III; Melanoma Stage IV

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response (MPR)

  Proportion of patients with an RVT (residual volume of viable tumor) of ≤10% remaining in post-therapy specimen using immunotherapy-specific pathologic assessment of neoadjuvant treated melanoma specimens.

  5 years (for population)

Secondary Outcomes (5)

• Number of Participants Experiencing Adverse Events Attributed to Treatment

  Up to 56 months

• Frequency of Delays in Surgery

  Up to 56 months

• Frequency of Cancellations of Surgery

  Up to 56 months

• Relapse-free Survival

  Up to 56 months

• Overall Survival (OS)

  Up to 56 months

Other Outcomes (2)

• Percentage of Circulating immune cells

  Up to 56 months

• Percentage of Intratumoral immune cells

  Up to 56 months

Study Arms (2)

Dostarlimab (TSR-042) (singly)

EXPERIMENTAL

Pre-Operative Phase: Dostarlimab (TSR-042) 500mg will be administered through an IV over 30 minutes, on Cycle 1 Day 1, and then again on Cycle 2 Day 1. Post-Operative Phase: Dostarlimab (TSR-042) 500mg will be administered through an IV over 30 minutes for 4 doses every 3 weeks (Cycles 3-4) and then 1000mg will be administered through an IV over 30 minutes every 6 weeks for 6 doses (Cycles 5-10) for approximately 48 weeks.

Drug: Dostarlimab (TSR-042) (singly)

Dostarlimab (TSR-042) and Cobolimab TSR-022 (combination)

EXPERIMENTAL

Pre-Operative Phase: Dostarlimab (TSR-042) 500mg and Cobolimab TSR-022 300mg will be administered through an IV over 30 minutes, on Cycle 1 Day 1 and then again on Cycle 2 Day 1. Post-Operative Phase: Dostarlimab (TSR-042) will be administered through an IV over 30 minutes for 4 doses every 3 weeks (Cycles 3-4), and then 1000mg will be administered through an IV over 30 minutes every 6 weeks for 6 doses (Cycles 5-10) for approximately 48 weeks. TSR-022 will not be administered.

Drug: Dostarlimab (TSR-042) and TSR-022 (combination)

Interventions

Dostarlimab (TSR-042) (singly) DRUG

If patients are randomized to Dostarlimab (TSR-042) alone, during the Pre-operative Phase, 500mg will be administered through an IV over 30 minutes, on Cycle 1 Day 1, and then again on Cycle 2 Day 1. Surgery will occur 1-4 weeks after completion of the pre-operative phase. During the Post-operative phase, Dostarlimab (TSR-042) 500mg will be administered through an IV over 30 minutes for 4 cycles every 3 weeks (Cycles 3-4), and then 1000mg will be administered through an IV over 30 minutes every 6 weeks (Cycles 5-10) for approximately 48 weeks.

Also known as: Dostarlimab

Dostarlimab (TSR-042) (singly)

Dostarlimab (TSR-042) and TSR-022 (combination) DRUG

If patients are randomized to the combination, Dostarlimab (TSR-042) and TSR-022, during the Pre-operative Phase, Dostarlimab (TSR-042) 500mg and TSR-022 300mg will be administered through an IV over 30 minutes on Cycle 1 Day 1 and then again on Cycle 2 Day 1. Surgery will occur 1-4 weeks after completion of the pre-operative phase. During the Post-operative Phase, Dostarlimab (TSR-042) 500mg will be administered through an IV over 30 minutes for 4 cycles every 3 weeks (Cycles 3-4) and then 1000mg will be administered through an IV over 30 minutes every 6 weeks for 6 doses (Cycles 5-10) for approximately 48 weeks.

Dostarlimab (TSR-042) and Cobolimab TSR-022 (combination)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• written informed consent for the study
• ≥ 18 years of age
• histologically or cytologically confirmed diagnosis of cutaneous or unknown primary melanoma (excluding uveal/choroidal and mucosal melanoma; although acral melanoma is included) belonging to one of the following AJCC 8th edition TNM stages:
• Tx or T1-4 AND
• N1b, or N1c, or N2b, or N2c, or N3b, or N3c AND/OR
• M1a or M1b
• Patients are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal and/or in-transit metastasis and/or oligometastasis; AND/OR at the time of clinical detected nodal and/or in-transit and/or oligometastatic recurrence; and may belong to any of the following groups:
• Primary melanoma with clinically apparent regional lymph node metastases; Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin; Clinically detected primary melanoma involving multiple regional nodal groups; Clinical detected nodal melanoma (if single site) arising from an unknown primary; In-transit and/or satellite metastases with or without regional lymph node involvement; Distant skin and/or in-transit and/or satellite metastases with or without regional lymph node involvement; Oligometastatic lung disease with or without regional lymph node involved permitted if deemed resectable at baseline NOTE: Determination of resectability must be made at baseline to be eligible for this neoadjuvant study.
• measurable disease based on RECIST 1.1
• must provide tumor tissue from a newly obtained core, punch, incisional or excisional tumor biopsy
• or 1 on the ECOG Performance Scale
• Demonstrate adequate organ function on screening labs obtained within 14 days of registration
• negative serum pregnancy test (females of childbearing potential)
• females of non-childbearing potential must be ≥45 years of age and has not had menses for \>1 year; if amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have an FSH value in the postmenopausal range; post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation (documented hysterectomy or oophorectomy)
• male subjects should agree to use an adequate method of contraception

You may not qualify if:

• Patients with uveal and/or mucosal melanoma histology are excluded (Patients with melanoma of unknown histology are permitted to enroll after discussion with Principal Investigator)
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Is receiving systemic immunosuppression with either corticosteroids (\>10mg daily prednisone equivalent) or other immunosuppressive medications) for active autoimmune disease: history of active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids (\>10mg daily prednisone or equivalent) or systemic immunosuppressive agents
• ≥ CTCAE grade 3 immune-related AE (irAE) experienced with prior immunotherapy (except, non-clinically significant lab abnormalities (elevations in lipase, amylase not associated with clinically significant disease etc.) even if ≥ CTCAE grade 3 may enroll if resolved at this time, or, development of autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤ 1)
• received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (except ≤ Grade 2 neuropathy)
• autoimmune disorders of Grade 4 while on prior immunotherapy
• known additional malignancy that is progressing or requires active treatment (except, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy)
• evidence of interstitial lung disease or active, non-infectious pneumonitis
• active infection requiring systemic therapy
• history or current evidence of any condition, therapy, or laboratory abnormality determined to be significant, in the opinion of the treating investigator
• known psychiatric or substance abuse disorders that would interfere with study compliance
• is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
• had a live vaccine within 30 days of initiating protocol therapy
• received prior therapy with an IDO inhibitor, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 and/or combination (including nivolumab, pembrolizumab or ipilimumab/nivolumab). Prior treatment with ipilimumab or interferon alfa is allowed.
• history of allergic or hypersensitivity reaction to components or excipients of Dostarlimab (TSR-042) and TSR-022, interferon alfa or ipilimumab

Sponsors & Collaborators

• Diwakar Davar: lead
• Tesaro, Inc.: collaborator

Study Sites (5)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Hillman Cancer Center Washington

Washington, Pennsylvania, 15301, United States

Location

Related Publications (1)

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Diwakar Davar, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: October 25, 2019
• Study Start: June 12, 2020
• Primary Completion: September 29, 2025
• Study Completion (Estimated): December 15, 2029
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)