NCT04722575

Combination or Sequence of Vemurafenib, Cobimetinib, and Atezolizumab in High-risk, Resectable Melanoma

"NEOadjuvant Plus Adjuvant Therapy With Combination or Sequence of Vemurafenib, cobImetinib, and atezolizuMab in Patients With High-risk, Surgically Resectable BRAF Mutated and Wild-type Melanoma"

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 95 (actual)
• Sponsor: Fondazione Melanoma Onlus · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Neoadjuvant plus adjuvant treatment with target therapy and immunotherapy given in combination or sequence may have an anti-tumour activity and may reduce the risk of relapse in patients with high-risk resectable melanoma (stage III B / C / D and oligometastatic stage IV).

Detailed description

Melanoma represents a considerable health burden and an ongoing area of unmet need in oncology. Despite melanoma accounts for only 1% of diagnosed skin cancers, it is the cause of most skin cancer-related deaths. Until recently, limited effective treatment options were available to patients with advanced melanoma. Historically, response rates to conventional chemotherapy and immunomodulation therapy (interleukin-2 or interferon-γ) have been reported at approximately 5-19%. Adjuvant immune checkpoint blockade (ICB) and target therapy improve outcomes of patients with high-risk resectable melanoma. It has recently been demonstrated that treatment with neoadjuvant and adjuvant targeted therapy (dabrafenib and trametinib) is associated with a high pathologic complete response (pCR) rate and improved outcomes over surgery alone. However, treatment with ICB has not been well studied in the neoadjuvant setting, despite preclinical studies suggesting that neoadjuvant administration of ICB is associated with improved survival and enhanced anti-tumour immune responses compared to the same therapy administered in the adjuvant setting. The advantage of neoadjuvant trials is the availability of blood and tumour tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumour microenvironment. Prospective neoadjuvant clinical trials with targeted (dabrafenib/trametinib combo) or immunotherapeutic agents (nivolumab alone or nivolumab/ipilimumab combo) and combinations are now running in a subgroup of highrisk melanoma patients with pooled overall promising preliminary results of high rates of pathologic complete responses (pCRs, 30-50%) and early data of positive correlation between pCR and relapse-free survival. Based on the available results to date, we aim to conduct a randomized, noncomparative phase II trial to define the role of neoadjuvant plus adjuvant target and immunotherapy, given in combination or sequence, in patients with high risk surgically resectable melanoma.This approach has the potential to define whether neoadjuvant treatment has antitumour activity and whether it reduces the risk of relapse after surgery.

Conditions

• Melanoma

Interventions

Type	Name	Description
DRUG	Cobimetinib 20 MG Oral Tablet	Cobimetinib 60 mg qd p.o. from week 1 to week 3 and week 5 to week 6. Week 4 off.
DRUG	Vemurafenib 240 Mg Oral Capsule	960 (arm A) /720 (arm B) mg bid p.o. from week 1 to week 6.
DRUG	Atezolizumab 1200 MG in 20 ML Injection	840 mg IV for 2 cycles for Arm B and C. After surgery in all arms 1200 mg IV for 52 weeks

Timeline

• Start date: 2020-10-12
• Primary completion: 2023-12-15
• Completion: 2027-06-01
• First posted: 2021-01-25
• Last updated: 2025-03-13

Locations

6 sites across 1 country: Italy