What side effects are associated with this type of intervention?

Common side effects of immune checkpoint inhibitors, which are similar to the anti-TIM-3 antibody TSR-022, include rash, diarrhea, fatigue, and nausea. Severe adverse events can include pneumonitis, colitis, hepatitis, endocrinopathies, and neurological toxicities. These side effects result from the immune system's activation against normal tissues, not just cancer cells.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of tumors, particularly those targeting immune checkpoints. Notable approvals include pembrolizumab (Keytruda) and nivolumab (Opdivo), both of which are PD-1 inhibitors used in various cancers such as melanoma, non-small cell lung cancer, and head and neck cancers. Additionally, ipilimumab (Yervoy), a CTLA-4 inhibitor, has been approved for melanoma. These treatments work by enhancing the immune system's ability to fight cancer, similar to the mechanism being studied with the anti-TIM-3 antibody TSR-022.

What other types of research exist?

Promising novel alternatives to TSR-022 for tumor patients include: 1) BR102, a bifunctional fusion protein targeting PD-L1 and TGF-β, which has shown efficacy and safety in preclinical studies. 2) Novel anti-CD20 monoclonal antibodies, which are being developed to improve immunotherapy response. 3) Lutetium Lu 177 vipivotide tetraxetan, a radioligand therapy that has shown clinical efficacy in prostate cancer and is being studied for broader applications. 4) ONC201, a selective DRD2 antagonist, which has shown promise in treating gliomas. These alternatives represent diverse mechanisms of action and therapeutic strategies in oncology.

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Monoclonal Antibodies

TSR-022 for Cancer

Phase 1

Recruiting

Research Sponsored by Tesaro, Inc.

Eligibility Criteria Checklist

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

Must have

Participant has histologically or cytologically proven advanced or metastatic NSCLC, and only squamous or nonsquamous cell carcinoma.

Participant has received no more than 2 prior lines of therapy for advanced or metastatic disease, which must only include a platinum-based doublet chemotherapy regimen and an anti-PD-1 or anti-PD-L1 antibody.

Must not have

Participant has a documented sensitizing EGFR, ALK, or ROS-1 mutation.

Participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing TSR-022, a new medicine that helps the immune system fight cancer by blocking a protein called TIM-3. TIM-3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that blocking TIM-3 with other treatments enhances the body's ability to fight tumors and suppress their growth. It targets patients with tumors, especially those who may not respond to standard treatments. The goal is to see if this medicine can help the immune system better attack cancer cells.

Who is the study for?

This trial is for adults with advanced solid tumors who've had no more than two prior therapies, including a platinum-based chemo and an anti-PD-(L)1 antibody. They must have measurable disease progression, adequate organ function, ECOG performance status of 0 or 1, and a life expectancy of at least three months. Women of childbearing potential need a negative pregnancy test.

What is being tested?

The AMBER study tests TSR-022, an anti-TIM-3 antibody for treating tumors. It has two parts: dose escalation to find the safe dosage (Part 1), and dose expansion to assess antitumor activity in combination with other drugs like TSR-042 or docetaxel or as monotherapy (Part 2).

What are the potential side effects?

Potential side effects may include immune-related reactions due to the immunotherapy nature of TSR-022 and other drugs being tested. These could involve inflammation in various organs, infusion reactions similar to allergic responses during drug administration, fatigue, blood disorders, 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 lung cancer is advanced or has spread, and it's either squamous or nonsquamous.

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I've had up to 2 treatments for my advanced cancer, including platinum chemotherapy and anti-PD-1/L1 therapy.

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My cancer has worsened after treatments including platinum chemotherapy and anti-PD-1 or PD-L1 therapy.

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I agree to provide a tissue sample from my cancer that was not treated with radiation.

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My advanced lung cancer can be measured by scans.

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I am 18 years old or older.

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I am fully active and can carry on all my pre-disease activities without restriction.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am expected to live at least 3 more months and can complete 4 cycles of a specific treatment.

Exclusion Criteria

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

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My cancer has a specific change in the EGFR, ALK, or ROS-1 gene.

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I have untreated brain metastases or cancer in the lining of my brain.

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My cancer does not show TIM-3 expression based on previous tests.

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I have an autoimmune disease that needed treatment in the last 2 years.

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I have or had lung inflammation that needed steroids for treatment.

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I am not eligible for docetaxel treatment according to local guidelines.

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I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

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I have not taken steroids or immunosuppressive medications in the last 3 days.

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I have been treated with specific immune or chemotherapy drugs before.

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I have had lung radiation of more than 30 gray in the last 6 months.

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I have or had another type of cancer.

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I have new or worsening brain or spinal cord cancer spread.

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I have not received any vaccines other than for COVID-19 within the last week.

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I stopped a PD-1/PD-L1/PD-L2 treatment due to side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

17Treatment groups

Experimental Treatment

Group I: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042Experimental Treatment2 Interventions

Group II: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapyExperimental Treatment1 Intervention

Group III: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapyExperimental Treatment1 Intervention

Group IV: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042Experimental Treatment2 Interventions

Group V: Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042Experimental Treatment2 Interventions

Group VI: Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxelExperimental Treatment2 Interventions

Group VII: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042Experimental Treatment2 Interventions

Group VIII: Part 2: Cohort A Melanoma-TSR-022 with TSR-042Experimental Treatment2 Interventions

Group IX: Part 2: Cohort A Melanoma-TSR-022 as monotherapyExperimental Treatment1 Intervention

Group X: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatinExperimental Treatment4 Interventions

Group XI: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatinExperimental Treatment4 Interventions

Group XII: Part 1f: TSR-022 in combination with TSR-042 and DocetaxelExperimental Treatment3 Interventions

Group XIII: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)Experimental Treatment2 Interventions

Group XIV: Part 1d: TSR-022 in combination with TSR-042 and TSR-033Experimental Treatment3 Interventions

Group XV: Part 1c: TSR-022 in combination with TSR-042Experimental Treatment2 Interventions

Group XVI: Part 1b: TSR-022 in combination with nivolumabExperimental Treatment2 Interventions

Group XVII: Part 1a: TSR-022 monotherapyExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pemetrexed

2014

Completed Phase 3

~5550

Cisplatin

2013

Completed Phase 3

~3120

TSR-033

2017

Completed Phase 1

~120

Docetaxel

1995

Completed Phase 4

~6550

Carboplatin

2014

Completed Phase 3

~6120

Nivolumab

2015

Completed Phase 3

~4010

0 / 23Eligibility 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

Immunotherapy, including treatments like anti-TIM-3 antibodies, enhances the body's immune response against cancer cells by blocking inhibitory pathways that tumors use to evade immune detection. This allows T-cells to effectively target and destroy cancer cells. For tumor patients, this targeted approach can lead to better outcomes and fewer side effects compared to traditional therapies.

Immunotherapy of heterogenous sarcomas: questions and strategies.Emerging and mechanism-based therapies for recurrent or metastatic Merkel cell carcinoma.