Atezolizumab + Bevacizumab for Melanoma

Recruiting at 2 trial locations

Overseen By Elizabeth Buchbinder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Elizabeth Buchbinder, MD

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: Until disease progression or adverse events

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments like bevacizumab or anti-PD-L1 therapies before, and there are restrictions on recent use of some medications like systemic immunosuppressive drugs and certain anticoagulants. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug atezolizumab for melanoma?

A study showed that atezolizumab, when used alone, had antitumor activity in patients with advanced melanoma, with a 35% response rate and a disease control rate of 46%. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab safe for treating melanoma?

The combination of Atezolizumab and Bevacizumab has been studied for safety in patients with advanced mucosal melanoma, showing it is generally safe for use. Common side effects of Atezolizumab include anemia (low red blood cell count), headache, and high blood pressure, while Bevacizumab can cause skin-related side effects like rash and itching. ^{1 2 6 7 8}

How is the drug combination of Atezolizumab and Bevacizumab unique for treating melanoma?

The combination of Atezolizumab and Bevacizumab is unique for treating melanoma because it targets both the immune system and blood vessel growth, offering a novel approach for advanced mucosal melanoma, which typically has low response rates to standard therapies. ^{1 2 8 9 10}

What is the purpose of this trial?

This research study is studying a combination of two drugs that change the immune system and tumor as a possible treatment for metastatic or unresectable stage III or IV cutaneous melanoma. The names of the study drugs involved in this study are: * Atezolizumab * Bevacizumab

Research Team

Elizabeth Buchbinder, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with stage III or IV cutaneous melanoma that can't be removed by surgery. Participants must not have used certain cancer drugs before, agree to use effective contraception, and provide a tumor sample. They should have normal organ function and no history of severe allergies to the drugs being tested or other major health issues.

Inclusion Criteria

My organ and bone marrow functions are normal.

I have had treatments for skin cancer but not with anti-PD-L1 or bevacizumab.

You must have a visible and measurable disease according to a specific set of guidelines.

Exclusion Criteria

You have had allergic reactions to similar drugs as atezolizumab or bevacizumab.

I have had leptomeningeal disease.

Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab and Bevacizumab intravenously every three weeks as part of the study treatment

Until disease progression or adverse events

Every 3 weeks (in-person)

Follow-up

Participants are monitored for survival and adverse events after treatment

Up to 5 years

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview The study tests combining Atezolizumab (which helps the immune system fight cancer) with Bevacizumab (which stops tumors from making new blood vessels) as a treatment for advanced skin cancer. The goal is to see if this drug duo works better together.

Participant Groups

Group I: Atezolizumab and Bevacizumab Experimental Treatment 2 Interventions

The research study procedures include screening for eligibility, study treatment including evaluations, a biopsy, and follow up visits. * Atezolizumab will be administered intravenously at a fixed predetermined dose every three weeks * Bevacizumab will be administered intravenously at a fixed predetermined dose every three weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis Study treatment will continue until study doctors decide to stop therapy due to criteria which may include disease progression, adverse events or changes in condition. Participants will be followed for survival health information following treatment until the study ends, which could be approximately 5 years from start of treatment

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Elizabeth Buchbinder, MD

Lead Sponsor

Trials

1

Recruited

30+

Elizabeth Buchbinder

Lead Sponsor

Trials

1

Recruited

30+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a phase 1b study involving 103 patients with advanced BRAFV600 wild-type melanoma who had progressed on anti-PD-1 therapy, the combination of cobimetinib and atezolizumab showed an objective response rate of 14.6% and a disease control rate of 38.8%.

The treatment was associated with significant adverse events, including diarrhea (72.8%), dermatitis acneiform (55.3%), and nausea (50.5%), highlighting the need for careful monitoring of side effects despite the limited efficacy observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. Sandhu, S., Atkinson, V., Cao, MG., et al.[2023]

In a phase 1b study involving 52 patients with advanced melanoma, first-line treatment with atezolizumab showed a confirmed objective response rate of 35%, indicating its effectiveness in this patient population.

Atezolizumab was found to be safe and tolerable, with common side effects including anemia and headache, and a median progression-free survival of 3.7 months, suggesting it can be a viable treatment option for advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. de Azevedo, SJ., de Melo, AC., Roberts, L., et al.[2022]

In the phase 3 COMBI-AD study involving 870 patients with resected stage III melanoma, the combination of dabrafenib and trametinib significantly improved relapse-free survival compared to placebo, leading to FDA approval for this treatment.

Despite the effectiveness in preventing relapse, the treatment did not result in significant changes in health-related quality of life as measured by the EQ-5D-3L questionnaire during or after the 12-month treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in patients with resected, high-risk melanoma with BRAFV600E or BRAFV600K mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial. Schadendorf, D., Hauschild, A., Santinami, M., et al.[2020]

In a phase 2 study of 185 patients with advanced BRAFV600-mutated melanoma, switching from targeted therapy (vemurafenib + cobimetinib) to atezolizumab after 3 months resulted in significantly shorter progression-free survival (PFS) compared to continuing targeted therapy (13.9 months vs. 5.9 months).

Despite the rapid loss of tumor control with the switch to atezolizumab, there was a numerical overall survival (OS) benefit at 2 years for patients who switched (67% vs. 58% for continued targeted therapy), suggesting potential long-term advantages of the immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial. Livingstone, E., Gogas, H., Kandolf-Sekulovic, L., et al.[2023]

In the phase III IMspire150 study involving 514 patients with BRAFV600-mutated advanced melanoma, the combination of atezolizumab, vemurafenib, and cobimetinib significantly improved progression-free survival (PFS) compared to the control group.

The study found that patients with elevated lactate dehydrogenase (LDH) and PD-L1- tumors benefited the most from atezolizumab treatment, indicating that LDH is a key predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma. Robert, C., Lewis, KD., Gutzmer, R., et al.[2022]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

In a study of 111 melanoma patients treated with immunotherapy or targeted therapy, the majority received immunotherapy, particularly anti-PD-1 treatments, with a total of 371 adverse events (AEs) reported.

The incidence of AEs was lower in patients receiving anti-PD-1 therapy, with only 15.3% experiencing severe (grade 3 to 4) AEs, which were more common in those on targeted therapies, highlighting the need for better reporting and understanding of both known and unknown AEs in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. Aguiar, JP., Cardoso Borges, F., Murteira, R., et al.[2021]

In a study of 43 patients with advanced mucosal melanoma, the combination of atezolizumab and bevacizumab resulted in a promising objective response rate of 45%, indicating significant efficacy as a first-line therapy.

The treatment demonstrated manageable safety, with 90.7% of patients experiencing treatment-related adverse events, though 25.6% had severe (grade ≥3) events, suggesting careful monitoring is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: A Multicenter, Open-Label, Single-Arm Phase II Study. Mao, L., Fang, M., Chen, Y., et al.[2023]

In a study of 1343 melanoma patients at high risk of recurrence, adjuvant bevacizumab improved the disease-free interval (DFI) with 51% of patients disease-free at 5 years compared to 45% in the observation group, indicating its efficacy in delaying recurrence.

However, there was no significant difference in overall survival (OS) between the bevacizumab and observation groups, with both showing a 5-year OS rate of 64%, suggesting that while bevacizumab may help prevent recurrence, it does not extend overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. Corrie, PG., Marshall, A., Nathan, PD., et al.[2022]

The combination of atezolizumab (anti-PD-L1) with BRAF and MEK inhibitors showed a high confirmed objective response rate of 71.8% in patients with BRAFV600-mutated metastatic melanoma, indicating strong anti-tumor activity.

This phase Ib study demonstrated that the triple therapy had manageable toxicity and resulted in a median duration of response of 17.4 months, with 39.3% of patients still responding after nearly 30 months, suggesting long-lasting effects of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. Sullivan, RJ., Hamid, O., Gonzalez, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in patients with resected, high-risk melanoma with BRAFV600E or BRAFV600K mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: A Multicenter, Open-Label, Single-Arm Phase II Study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. [2022]