What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving PD-1 inhibitors like nivolumab and pembrolizumab, are associated with immune-related adverse events. These include skin reactions (rash, pruritus), endocrine issues (thyroid dysfunction), and gastrointestinal problems (diarrhea, colitis). Combination therapies, such as nivolumab plus ipilimumab, often result in higher toxicity rates, including severe immune-related adverse events like pneumonitis, hepatitis, and endocrinopathies.

What prior FDA approvals exist?

The FDA has approved several PD-1 inhibitors for the treatment of melanoma. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are notable examples, both of which have shown efficacy in treating advanced melanoma. Pembrolizumab is approved for use as a single agent and in combination with ipilimumab, a CTLA-4 inhibitor. Nivolumab is also approved for use alone and in combination with ipilimumab. These treatments are similar to the anti-PD-1 inhibitor TSR-042 being studied in the trial. While the combination of PD-1 inhibitors with TIM-3 inhibitors like TSR-022 is still investigational, the existing approvals highlight the effectiveness of targeting the PD-1 pathway in melanoma treatment.

What other types of research exist?

Promising alternatives for melanoma treatment in 2024 include: 1) Nivolumab combined with Ipilimumab, which has shown higher response rates in various melanoma subtypes. 2) Pembrolizumab, another anti-PD-1 monoclonal antibody, which has demonstrated efficacy in multiple trials. 3) Talimogene laherparepvec (T-VEC) combined with Pembrolizumab, which has shown promising results in advanced melanoma. These therapies have demonstrated significant activity and could be considered as novel alternatives.

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PD-1 Inhibitor

PD-1 Inhibitor vs. PD-1 + TIM-3 Inhibitors for Melanoma

Phase 2

Recruiting

Led By Diwakar Davar, MD

Research Sponsored by Diwakar Davar

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed diagnosis of cutaneous or unknown primary melanoma (excluding uveal/choroidal and mucosal melanoma; although acral melanoma is included) belonging to specific AJCC 8th edition TNM stages

N1b, or N1c, or N2b, or N2c, or N3b, or N3c AND/OR M1a

Must not have

Known additional malignancy that is progressing or requires active treatment

Autoimmune disorders of Grade 4 while on prior immunotherapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 56 months

Awards & highlights

Summary

This trial tests Dostarlimab alone or with TSR-022 in patients with advanced but operable melanoma. These drugs help the immune system attack cancer by preventing cancer cells from hiding. The goal is to see if these treatments improve outcomes before and after surgery.

Who is the study for?

Adults with operable melanoma, including primary melanoma with regional metastasis or recurrence, are eligible for this trial. They must have adequate organ function and provide a recent tumor biopsy. Pregnant women and individuals on systemic immunosuppression or with certain autoimmune diseases, other active cancers, or severe psychiatric issues cannot participate.

What is being tested?

The study is testing the effectiveness of Dostarlimab (TSR-042) alone versus its combination with Cobolimab (TSR-022) in treating melanoma before surgery. Participants will be randomly assigned to receive one of these two treatment options.

What are the potential side effects?

Potential side effects include immune-related reactions that could affect various organs, infusion-related symptoms like fever or chills, fatigue, possible hormonal gland problems leading to hormone deficiencies, skin reactions at injection sites and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My melanoma is not related to the eye or mucous membranes but confirmed by a lab test.

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My cancer has spread to nearby lymph nodes or distant parts of my body.

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I am 18 years old or older.

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have another cancer that is getting worse or needs treatment.

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I had a severe autoimmune reaction to previous immunotherapy.

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I have had a severe side effect from previous immunotherapy.

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My cancer has spread to my brain or spinal cord.

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I have previously been treated with specific inhibitors or immunotherapies.

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I am taking medication to suppress my immune system for an autoimmune disease.

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I have a lung condition not caused by an infection.

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I haven't had chemotherapy, targeted therapy, or radiation in the last 2 weeks and have recovered from any side effects.

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I have been diagnosed with HIV.

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I have not received a live vaccine in the last 30 days.

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I am currently on medication for an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 56 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 56 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 56 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Major Pathologic Response (MPR)

Secondary study objectives

Frequency of Cancellations of Surgery

Frequency of Delays in Surgery

Number of Participants Experiencing Adverse Events Attributed to Treatment

+2 more

Other study objectives

Percentage of Circulating immune cells

Percentage of Intratumoral immune cells

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dostarlimab (TSR-042) and TSR-022 (combination)Experimental Treatment1 Intervention

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. 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.

Group II: Dostarlimab (TSR-042) (singly)Experimental Treatment1 Intervention

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.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for melanoma include immune checkpoint inhibitors that target proteins such as PD-1 and TIM-3. PD-1 inhibitors, like nivolumab and pembrolizumab, work by blocking the PD-1 receptor on T cells, preventing cancer cells from evading the immune response. TIM-3 inhibitors, which are still under investigation, aim to enhance the immune response by targeting another checkpoint that regulates T cell activity. Combining PD-1 and TIM-3 inhibitors, as in the TSR-042/TSR-022 trial, may provide a more robust activation of the immune system, potentially leading to better control of melanoma. These treatments are crucial for melanoma patients as they offer a targeted approach to boost the body's own defenses against cancer, potentially improving outcomes and survival rates.

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Who is running the clinical trial?

Tesaro, Inc.Industry Sponsor

56 Previous Clinical Trials

10,462 Total Patients Enrolled

2 Trials studying Melanoma

45 Patients Enrolled for Melanoma

Diwakar DavarLead Sponsor

11 Previous Clinical Trials

358 Total Patients Enrolled

8 Trials studying Melanoma

272 Patients Enrolled for Melanoma

Diwakar Davar, MD5.01 ReviewsPrincipal Investigator - UPMC Hillman Cancer Center

University of Pittsburgh

7 Previous Clinical Trials

207 Total Patients Enrolled

6 Trials studying Melanoma

181 Patients Enrolled for Melanoma

5Patient Review

Dr. Davar is always so patient with me and takes the time to ensure I understand everything. After my melanoma diagnosis, it's been difficult to process information, but he is very thorough and caring.