Atezolizumab + Bevacizumab for Melanoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs: atezolizumab (Tecentriq, an immunotherapy drug) and bevacizumab (Avastin, an anti-angiogenesis drug), to determine their effectiveness in treating advanced melanoma. The study targets individuals whose melanoma has spread or cannot be surgically removed, specifically those with stage III or IV melanoma who have not previously received these drugs. The trial aims to assess how well these drugs work together to control or reduce the cancer. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of atezolizumab and bevacizumab has a manageable safety profile. In patients with advanced mucosal melanoma, this combination was generally well-tolerated. High blood pressure and tiredness were the most common side effects, each affecting about 30% of patients. While important to consider, these side effects are common and manageable with proper medical care. Overall, evidence suggests that this treatment combination is reasonably safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about the combination of Atezolizumab and Bevacizumab for melanoma because it represents a novel approach by harnessing the body’s immune system alongside inhibiting blood vessel growth in tumors. Atezolizumab is an immunotherapy that boosts the immune system to better recognize and attack cancer cells, while Bevacizumab cuts off the tumor's blood supply by targeting a protein called VEGF. Unlike standard treatments like chemotherapy, which attack cancer cells directly, this combination aims to both empower the immune response and starve the tumor, potentially leading to more effective and lasting results.

What evidence suggests that this treatment might be an effective treatment for melanoma?

Research has shown that the combination of the drugs atezolizumab and bevacizumab, which participants in this trial will receive, offers promising results for treating advanced melanoma, a serious type of skin cancer. Earlier studies demonstrated improved outcomes for patients with advanced mucosal melanoma using this drug pair. The combination proved effective and had a safety profile manageable for most patients. In one study, about 26% of patients experienced a reduction or disappearance of their cancer. Although side effects exist, most patients manage the treatment well. These findings suggest that this treatment could be effective for people with advanced melanoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Elizabeth Buchbinder, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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 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 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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39757723/

3-year survival update and multi-omics analysis Background: Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi-centre phase II study. This report updates 3- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9623232/

Atezolizumab plus Bevacizumab in Patients with ... Conclusions: Atezolizumab in combination with bevacizumab showed promising efficacy and manageable safety in patients with advanced mucosal melanoma.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9525

Atezolizumab plus bevacizumab in patients with ... Overall, 90.7% (39/43) of patients experienced treatment-related adverse events, and 25.6% (11/43) experienced grade ≥ 3 events. Conclusions: ...

4. roche.com roche.com/media/releases/med-cor-2017-06-03

Roche presents new data for TECENTRIQ® (atezolizumab) ... Specifically, TECENTRIQ plus Avastin resulted in an Overall Response Rate (ORR) of 26% in all-crossover patients (28% in crossover post- ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ctm2.70169

Atezolizumab plus bevacizumab in patients with ... Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi-centre phase II study.

6. tecentriq-hcp.com tecentriq-hcp.com/hcc/patient-reported-outcomes.html

Patient-reported outcomes - TECENTRIQ-HCP.com The most common adverse reactions (rate ≥20%) in patients who received TECENTRIQ in combination with bevacizumab for HCC were hypertension (30%), fatigue/ ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1915745

Atezolizumab plus Bevacizumab in Unresectable ... The IMbrave150 trial showed significantly better overall survival and progression-free survival outcomes with atezolizumab plus bevacizumab than ...