Cobimetinib and atezolizumab administered prior to surgery eliminated or shrunk tumors in 70% of patients with melanoma enrolled in the NeoACTIVATE trial. Results were published by Hieken et al in Nature Communications.
Background
Melanoma of the skin is the fifth most common cancer type in the United States, according to the National Cancer Institute. About 100,000 U.S. patients will be diagnosed with melanoma in 2024, and about 1.5 million U.S. patients are currently living with the disease. The researchers explained that BRAF-mutated melanoma accounts for about 50% of melanoma cases. However, certain targeted therapies have been shown to be effective at countering the mutation.
This was one of the first clinical trials to explore the use of targeted therapy plus immunotherapy prior to surgery in patients with and without BRAF-mutated melanoma.
Study Methods or Results
In the phase II NeoACTIVATE trial, the researchers assigned patients with stage III melanoma to receive two combinations of the targeted therapies vemurafenib and cobimetinib and the immunotherapy atezolizumab prior to surgery followed by additional immunotherapy postsurgery.
The trial included three arms. In arm A, the patients with BRAF-mutated melanoma received a combination of vemurafenib, cobimetinib, and atezolizumab prior to surgery. In arm B, the patients without the BRAF mutation received cobimetinib and atezolizumab prior to surgery. Both arms then received atezolizumab following surgery. Vemurafenib and cobimetinib are designed to fight cancer by blocking or turning off signals in specific types of cancer cells and may also enhance the immune response. Atezolizumab is capable of triggering the body’s immune system to help fight cancer.
The researchers discovered that 67% of the patients with BRAF-mutated melanoma demonstrated a complete pathologic response and 20% of them had a partial response. In the group with patients without the BRAF mutation, the results were not as stark; however, they still demonstrated the potential of the drug combination. About 33% of those without the BRAF mutation experienced a complete or nearly complete pathologic response. Another 20% of them had a partial response.
“We saw that about two-thirds of the patients in one arm of the trial had no remaining tumor at all at the time of their surgery,” detailed senior study author Matthew S. Block, MD, PhD, an immunologist and medical oncologist at the Mayo Clinic Comprehensive Cancer Center as well as Leader of the Stand Up To Cancer (SU2C) Catalyst Research Team.
Assessing both groups together, the novel drug combination completely or nearly completely eliminated the tumors in 50% of the trial participants and significantly shrunk the tumors in an additional 20% of the participants.
In arm C of the trial, the patients are currently receiving a combination of atezolizumab and the immunotherapy drug tiragolumab. The researchers hope to complete enrollment for this treatment arm in the coming months.
Conclusions
“We believe these results support the concept that a short course of certain drug combinations given before surgery can help a substantial number of patients,” highlighted lead study author Tina J. Hieken, MD, a surgical oncologist at the Mayo Clinic Comprehensive Cancer Center and Clinical Lead of the Stand Up To Cancer (SU2C) Catalyst Research Team.
The findings revealed that better understanding the effects of the novel drug combination may lead to improved treatment among patients with melanoma whose cancers don’t respond well to immunotherapy alone. They plan to conduct further research and clinical trials to uncover possible biological clues that may help physicians select the best individualized treatment options in patients with melanoma.
“We’re very excited that this research team’s work is helping us learn more about the potential promise of these therapies,” said Ira Mellman, PhD, Vice President of Cancer Immunology at Genentech and a member of the Roche Group. “We hope that these promising results will transform into therapies that can help many patients with melanoma,” he suggested.
“Stand Up To Cancer’s support of this trial—in collaboration with our donor Genentech, a member of the Roche Group—was critical as we seek to understand and potentially treat this common cancer in new and innovative ways,” emphasized Julian Adams, PhD, President and Chief Executive Officer of SU2C. “Considering the number of [patients] impacted by melanoma, these results could significantly help improve survival rates,” he concluded.
Disclosure: The research in this trial was supported by SU2C. For full disclosures of the study authors, visit ncbi.nlm.nih.gov.
