What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving immune checkpoint inhibitors such as nivolumab, ipilimumab, and pembrolizumab, can lead to a range of side effects. These include skin reactions (e.g., rash, pruritus), gastrointestinal issues (e.g., diarrhea, colitis), and endocrine disorders (e.g., hypothyroidism, adrenal insufficiency). More severe but less common side effects include immune-related adverse events like pneumonitis, hepatitis, and nephritis. Combination therapies tend to have higher rates of severe toxicities compared to single-agent treatments, necessitating careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several immunotherapy drugs for the treatment of melanoma, focusing on enhancing the immune system's ability to target cancer cells. Notable approvals include ipilimumab (a CTLA-4 inhibitor), nivolumab, and pembrolizumab (both PD-1 inhibitors). Combination therapies such as nivolumab plus ipilimumab have also been approved, showing improved efficacy in treating advanced melanoma. These treatments work by blocking immune checkpoints, thereby boosting the immune response against melanoma cells.

What other types of research exist?

Promising novel alternatives to cancer immunotherapy combinations for melanoma patients in 2024 include chimeric antigen receptor (CAR)-T cell therapies and new experimental immunotherapies being tested in clinical trials. These approaches aim to enhance the immune system's ability to recognize and destroy cancer cells more effectively. Patients should consider enrolling in clinical trials to access these cutting-edge treatments.

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Checkpoint Inhibitor

Immunotherapy Combinations for Melanoma

Phase 1 & 2

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

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

Must have

For Cohort 2: ECOG PS of 0 or 1

For Cohort 1: Histologically confirmed resectable Stage III melanoma according to AJCC-8 and no history of in-transit metastases within the last 6 months

Must not have

For Cohort 2: Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment

For Cohort 2: Prior allogeneic stem cell or solid organ transplantation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up randomization up to approximately 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing new treatments to help the immune system fight cancer in patients with advanced melanoma. It includes patients who have not yet received treatment for their melanoma. The goal is to find effective and safe options for these patients.

Who is the study for?

This trial is for adults with Stage III melanoma eligible for surgery or those with Stage IV melanoma who've had limited treatment. Participants must have good organ function, no HIV/Hepatitis B/C unless controlled, and a performance status showing they can handle daily activities. Exclusions include certain types of melanoma, prior immunotherapy or stem cell transplants, active autoimmune diseases, and uncontrolled symptoms related to cancer.

What is being tested?

The study tests combinations of cancer immunotherapies like Nivolumab, Ipilimumab, RO7247669 (two doses), Atezolizumab, and Tiragolumab in patients new to these treatments. It's flexible; new arms may open/close based on results or safety concerns. The goal is to assess how well the treatments work (efficacy), their safety profile, and how the body processes them.

What are the potential side effects?

Possible side effects from the tested drugs include immune-related reactions that could affect organs like the liver or intestines, skin issues such as rashes or itching, fatigue, hormonal gland problems which might require hormone therapy replacement and infusion-related reactions during drug administration.

Eligibility Criteria

Inclusion Criteria

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

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

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I have Stage III melanoma that can be surgically removed and no recent spread to nearby skin.

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

Exclusion Criteria

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

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I have an immune system disorder or need medication that weakens my immune system.

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

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I have had cancer spread to areas between the primary tumor and nearby lymph nodes in the last 6 months.

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I haven't taken any immune-boosting drugs within the last 4 weeks or 5 half-lives before starting the study.

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I need frequent procedures to remove fluid from my chest, heart area, or abdomen.

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I have or had an autoimmune disease or immune deficiency.

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My melanoma has spread to distant parts of my body.

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I have had radiotherapy before.

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I have previously received immunotherapy or other treatments for melanoma.

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I have an immune system disorder or need medication that weakens my immune system.

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I haven't taken any experimental drugs in the last 28 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ randomization up to approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~randomization up to approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and randomization up to approximately 5 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

Objective Response Rate (ORR) for Cohort 2

Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review

Secondary study objectives

Disease Control for Cohort 2

Duration of Response (DOR) for Cohort 2

Event-Free Survival (EFS) for Cohort 1

+9 more

Side effects data

From 2019 Phase 3 trial • 1225 Patients • NCT02008227

36%

Fatigue

35%

Alopecia

24%

Diarrhoea

23%

Nausea

23%

Decreased appetite

22%

Anaemia

20%

Asthenia

19%

Cough

19%

Dyspnoea

16%

Myalgia

15%

Neutropenia

14%

Constipation

14%

Oedema peripheral

12%

Pyrexia

11%

Stomatitis

11%

Vomiting

11%

Neuropathy peripheral

10%

Arthralgia

Neutrophil count decreased

Rash

Headache

Dysgeusia

Paraesthesia

Pain in extremity

Mucosal inflammation

Back pain

Peripheral sensory neuropathy

Insomnia

Pneumonia

Febrile neutropenia

Lacrimation increased

Abdominal pain

Dry skin

Dizziness

Malaise

Urinary tract infection

Weight decreased

Haemoptysis

Nail disorder

Chest pain

Nasopharyngitis

Musculoskeletal pain

Bronchitis

Productive cough

Upper respiratory tract infection

Pruritus

Influenza like illness

Alanine aminotransferase increased

Aspartate aminotransferase increased

Syncope

Dehydration

Atrial fibrillation

Lower respiratory tract infection

Lung infection

Respiratory tract infection

Acute kidney injury

Chronic obstructive pulmonary disease

Pleural effusion

Depression

Musculoskeletal chest pain

100%

80%

60%

40%

20%

Study treatment Arm

Docetaxel

Atezolizumab

Awards & Highlights

No Placebo-Only Group

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

Trial Design

7Treatment groups

Experimental Treatment

Active Control

Group I: Cohort 2: RO7247669 2100 mg + TiragolumabExperimental Treatment2 Interventions

Cohort 2 participants in RO7247669 plus tiragolumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Group II: Cohort 1: RO7247669 600 mg + TiragolumabExperimental Treatment2 Interventions

Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Group III: Cohort 1: RO7247669 600 mgExperimental Treatment1 Intervention

Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Group IV: Cohort 1: RO7247669 2100 mg + TiragolumabExperimental Treatment2 Interventions

Group V: Cohort 1: RO7247669 2100 mgExperimental Treatment1 Intervention

Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Group VI: Cohort 1: + Atezolizumab + TiragolumabExperimental Treatment2 Interventions

Cohort 1 participants in the atezolizumab plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Group VII: Cohort 1: Nivolumab + IpilimumabActive Control2 Interventions

Cohort 1 participants in the nivolumab plus ipilimumab arm will receive treatment for 2 cycles (6 weeks) on Day 1 of each cycle (cycle length 21 days) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

RO7247669 2100 mg

2022

Completed Phase 2

~110

Atezolizumab

2016

Completed Phase 3

~5860

Tiragolumab

2019

Completed Phase 3

~1390

RO7247669 600 mg

2022

Completed Phase 2

~110

0 / 14Eligibility 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, particularly advanced stages, involve immune checkpoint inhibitors such as PD-1 inhibitors (nivolumab, pembrolizumab) and CTLA-4 inhibitors (ipilimumab). These therapies work by blocking proteins that inhibit T-cell activity, thereby enhancing the immune system's ability to recognize and destroy cancer cells. PD-1 inhibitors prevent the PD-1 protein on T cells from binding to PD-L1 on cancer cells, which would otherwise deactivate the T cells. CTLA-4 inhibitors block the CTLA-4 protein, which downregulates immune responses. This dual blockade can lead to a more robust and sustained immune attack on melanoma cells, improving patient outcomes. Understanding these mechanisms is crucial for melanoma patients as it highlights the importance of immune system engagement in their treatment strategy.