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Monoclonal Antibodies

Combination Therapy for Melanoma

Phase 2

Recruiting

Led By Matthew S Block

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

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

Must have

Age >= 18 years

High-risk stage III melanoma as defined by recurrent nodal metastasis, clinically detectable nodal metastasis, or metastatic involvement of more than one nodal basin

Must not have

Uncontrolled intercurrent illness including ongoing or active infection

Received anticancer treatments or investigational agents during pre-registration period

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of immunotherapies and targeted therapies to treat high-risk stage III melanoma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Who is the study for?

This trial is for adults over 18 with high-risk stage III melanoma that can be surgically removed. Participants must have a specific BRAFV600 mutation, agree to provide tissue samples, and not use other cancer treatments during the study. They should not have certain health conditions like active psoriasis or uncontrolled diabetes, nor should they be pregnant or unwilling to use contraception.

What is being tested?

The trial tests how well vemurafenib and cobimetinib (which block enzymes for cell growth) work with atezolizumab and tiragolumab (monoclonal antibodies boosting immune response against cancer). It aims to see if this combination is more effective in treating patients than current methods.

What are the potential side effects?

Possible side effects include allergic reactions, inflammation of organs due to immune response, liver issues from enzyme blockers, fatigue, skin rash, joint pain from targeted therapies and immunotherapies. Each patient may experience different side effects.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My melanoma has spread to more than one lymph node area.

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My melanoma is confirmed to be at stage III.

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I am willing to stop any cancer treatments before joining the study.

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My condition can be treated with surgery.

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My melanoma has been tested for the BRAFV600 mutation.

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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 do not have any uncontrolled illnesses or active infections.

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I have received cancer treatments or been part of a study before registering.

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I have had melanoma spread beyond the lymph nodes or to my brain.

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I have a history of specific eye retina problems.

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I am not on any systemic immunosuppressive medications or required diets that are not allowed.

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I have had a previous transplant of stem cells or an organ.

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I do not have major heart issues, stroke, severe bleeding, uncontrolled diabetes, or serious mental health/social problems.

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I will be taking medication that can affect my heart's rhythm.

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I am not on any experimental drugs for my cancer.

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I need treatment for my active psoriasis.

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I have had major surgery recently or expect to need one soon.

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I have a significant liver condition.

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My melanoma is suspected to have spread beyond the lymph nodes.

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I have a history of nutrient absorption problems or significant metabolic issues.

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I have had radiation therapy for melanoma.

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I have a history of certain lung and autoimmune diseases.

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I have signs of an infection or have recently used antibiotics.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Median recurrence-free (RFS) rate (adjuvant phase)

Melanoma

Pathologic complete response rate in patients with stage III BRAFwt (wild type) melanoma (neoadjuvant phase)

Secondary study objectives

Cognitive Therapy

Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) (neoadjuvant phase)

Other study objectives

Changes in T cell receptor clonality

Changes in the concentration of circulating tumor deoxyribonucleic acid (DNA) during neoadjuvant treatment

Molecular features of melanomas and the tumor immune microenvironment evaluated with multiplexed immunohistochemistry (mIHC) and ribonucleic acid sequencing (RNASeq)

+1 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C (atezolizumab, tiragolumab)Experimental Treatment2 Interventions

Patients with BRAF wild-type or BRAF mutant melanoma receive atezolizumab IV over 30-60 minutes and tiragolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B - CLOSED (cobimetinib, atezolizumab)Experimental Treatment2 Interventions

Patients receive cobimetinib as in Arm A and atezolizumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients undergo surgery then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm A - CLOSED (vemurafenib, cobimetinib, atezolizumab)Experimental Treatment3 Interventions

Patients receive vemurafenib PO BID on days 1-28 and cobimetinib PO QD on days 1-21. Patients also receive atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15 of cycles 2 and 3. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients undergo surgery then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

Cobimetinib

2017

Completed Phase 3

~3630