What is the mechanism of action of this treatment?

Common treatments for tumors, particularly immunotherapies like Vibostolimab (an anti-TIGIT monoclonal antibody), work by enhancing the body's immune response against cancer cells. Vibostolimab blocks the TIGIT pathway, which tumors use to evade immune detection. By inhibiting this pathway, it reactivates T-cells to recognize and destroy cancer cells. This targeted approach is significant for tumor patients as it boosts the immune system's ability to fight cancer, potentially improving outcomes and reducing side effects compared to traditional therapies.

What side effects are associated with this type of intervention?

Common side effects of immune checkpoint inhibitors such as pembrolizumab and durvalumab include fatigue, musculoskeletal pain, decreased appetite, pruritus (itching), diarrhea, nausea, rash, pyrexia (fever), cough, dyspnea (difficulty breathing), constipation, and abdominal pain. Severe adverse events can include pneumonia, pneumonitis, and immune-mediated reactions requiring additional treatments like steroids or other immunosuppressive agents.

What prior FDA approvals exist?

The FDA has approved several monoclonal antibodies and immune checkpoint inhibitors for the treatment of tumors. Notable examples include Pembrolizumab (Keytruda) and Nivolumab (Opdivo), which target the PD-1 receptor, and Ipilimumab (Yervoy), which targets CTLA-4. These drugs have been approved for various cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma. Additionally, Atezolizumab (Tecentriq) targets PD-L1 and has been approved for urothelial carcinoma and non-small cell lung cancer. These treatments work by enhancing the immune system's ability to recognize and destroy cancer cells, similar to the mechanism being studied for Vibostolimab, an anti-TIGIT monoclonal antibody.

What other types of research exist?

Promising novel alternatives to Vibostolimab for tumor patients in 2024 include: 1) Pembrolizumab (anti-PD-1) combined with other agents like pemetrexed and carboplatin, which has shown efficacy in various cancers including non-small cell lung cancer. 2) Atezolizumab (anti-PD-L1) combined with bevacizumab and other agents, which has been effective in renal cell carcinoma and other solid tumors. 3) Ipilimumab (anti-CTLA-4) combined with nivolumab (anti-PD-1), which has demonstrated long-term survival benefits in metastatic melanoma and renal cell carcinoma. 4) Talimogene laherparepvec (T-VEC) combined with pembrolizumab, which has shown promise in advanced melanoma. These alternatives offer different mechanisms of action and have shown significant clinical benefits in various tumor types.

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Checkpoint Inhibitor

Vibostolimab + Pembrolizumab for Advanced Cancer

Phase 1

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

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

Must have

Has an Eastern Cooperative Oncology Group performance status of 0 to 1

Females must not be pregnant

Must not have

Has received previous treatment with an immunomodulatory agent (e.g., anti-programmed cell death 1, anti-programmed cell death ligand 1 or cytotoxic T-lymphocyte-associated protein 4) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event

Is on chronic systemic steroid therapy in excess of replacement doses or on any other form of immunosuppressive medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called vibostolimab, alone or with another drug called pembrolizumab, in adults with advanced cancers who have no other treatment options. The goal is to see if these drugs are safe and effective in helping the immune system fight cancer.

Who is the study for?

This trial is for adults with advanced solid tumors and no remaining treatment options expected to help. Participants must have measurable disease, be in good physical condition, not pregnant, agree to use contraception, and provide a tumor sample. Specific groups include Chinese from mainland China or Japanese descent with certain cancers who haven't had anti-PD-1/PD-L1 therapy.

What is being tested?

The study tests vibostolimab alone and combined with pembrolizumab (with or without chemotherapy) in metastatic solid tumors. It aims to find the safest dose that can be given (RPTD), assess how the body processes these drugs, and evaluate their effectiveness against cancer.

What are the potential side effects?

Potential side effects may include immune-related reactions due to immunotherapy agents like pembrolizumab/vibostolimab which could affect organs; infusion reactions; fatigue; digestive issues; blood disorders; increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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I can carry out all my usual activities without help.

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I am not pregnant.

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I have a metastatic solid tumor with no beneficial treatment options available.

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My cancer has spread and this was confirmed by a lab test.

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I have stage IV non-squamous NSCLC confirmed by tests.

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I have provided a sample of my tumor for testing.

Exclusion Criteria

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

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I stopped an immune therapy due to a severe side effect.

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I am taking high doses of steroids or other drugs that weaken my immune system.

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I cannot or will not take folic acid or Vitamin B12 supplements.

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I have cancer that has spread to my brain or spinal cord.

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I am currently being treated for an infection.

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I have had pneumonitis treated with steroids.

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I have had a bone marrow or organ transplant.

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I am HIV positive or have active Hepatitis B or C.

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I have been treated with a drug targeting the TIGIT receptor before.

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I have interstitial lung disease.

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I have fluid buildup in my abdomen or around my lungs.

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I still experience side effects from cancer treatment received over 4 weeks ago.

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I haven't had cancer treatment or major surgery in the last 4 weeks.

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

11Treatment groups

Experimental Treatment

Group I: vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposideExperimental Treatment5 Interventions

Participants will receive 200 mg vibostolimab in combination with 200 mg pembrolizumab, plus the investigator's choice of Area Under Curve (AUC) 5 mg/mL/min carboplatin OR 75 mg/m\^2 cisplatin on Day 1 of each 21-day cycle plus 100 mg/m\^2/day etoposide on Days 1-3 of each 21-day cycle for up to 4 cycles. Maintenance therapy with 200 mg vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day cycle will continue for up to an additional 31 cycles. A participant will be allowed to switch from cisplatin to carboplatin in the event of an adverse event (AE), ineligibility for further cisplatin therapy, and/or the investigator considers switching to carboplatin to be in the best interest of the participant.

Group II: vibostolimab Dose 2 Japanese cohortExperimental Treatment2 Interventions

Japanese participants will be randomized to receive a fixed dose (Dose 2) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Group III: vibostolimab Dose 1 Japanese cohortExperimental Treatment2 Interventions

Japanese participants will be randomized to receive a fixed dose (Dose 1) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Group IV: vibostolimab +pembrolizumab+pemetrexed+carboplatinExperimental Treatment4 Interventions

Participants will receive a fixed dose of vibostolimab in combination with 200 mg pembrolizumab, 500 mg/m\^2 pemetrexed, and Area Under Curve (AUC) 5 mg/mL/min carboplatin on Day 1 of each 21-day infusion cycle for up to 4 cycles followed by maintenance therapy with a fixed dose of vibostolimab in combination with 200 mg pembrolizumab and 500 mg/m\^2 pemetrexed on Day 1 of each 21-day infusion cycle for up to an additional 31 cycles.

Group V: vibostolimab + pembrolizumabExperimental Treatment2 Interventions

During an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD of vibostolimab has been established. The RPTD will be established based on the number of DLTs at each dose level. Once the RPTD of vibostolimab is established, participants will continue receiving the RPTD of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Group VI: vibostolimabExperimental Treatment1 Intervention

During an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of vibostolimab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD has been established. The RPTD will be established based on the number of dose limiting toxicities (DLTs) at each dose level. Once the RPTD is established, participants will continue receiving the RPTD of vibostolimab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Group VII: pembrolizumab/vibostolimab coformulation China cohortExperimental Treatment1 Intervention

Participants from mainland China will receive a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles.

Group VIII: pembrolizumab/vibostolimab coformulationExperimental Treatment1 Intervention

Participants will receive a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles.

Group IX: Randomized dose 2 comparison cohortExperimental Treatment2 Interventions

Participants will be randomized to receive a fixed dose (Dose 2) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Group X: Randomized dose 1 comparison cohortExperimental Treatment2 Interventions

Participants will be randomized to receive a fixed dose (Dose 1) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Group XI: Advanced solid tumor cohortExperimental Treatment2 Interventions

Participants will receive the RPTD of vibostolimab monotherapy or the RPTD of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

vibostolimab

2016

Completed Phase 1

~470

pembrolizumab

2017

Completed Phase 3

~6070

pemetrexed

2005

Completed Phase 3

~5000

carboplatin

2010

Completed Phase 3

~4790

pembrolizumab/vibostolimab coformulation

2016

Completed Phase 1

~470

cisplatin

1997

Completed Phase 3

~3290

etoposide

1994

Completed Phase 3

~9300

0 / 19Eligibility 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

Common treatments for tumors, particularly immunotherapies like Vibostolimab (an anti-TIGIT monoclonal antibody), work by enhancing the body's immune response against cancer cells. Vibostolimab blocks the TIGIT pathway, which tumors use to evade immune detection. By inhibiting this pathway, it reactivates T-cells to recognize and destroy cancer cells. This targeted approach is significant for tumor patients as it boosts the immune system's ability to fight cancer, potentially improving outcomes and reducing side effects compared to traditional therapies.

Inclusion body myositis: update.