CHECKMATE 204: NIVO plus IPI found safe, effective for melanoma patients with brain metastases

In patients with melanoma, treatment of brain metastases with nivolumab (NIVO)—a fully human immunoglobulin (Ig) G4 monoclonal antibody—plus ipilimumab (IPI)—also a monoclonal antibody, achieved high objective responses (56%) and exhibited favorable safety, according to results from the CheckMate 204 study, which were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

“One of the great promises of immunotherapy is the ability to combine agents that can synergistically reactivate antitumor immunity,” said study co-author Michael B. Atkins, MD, deputy director, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC.

Georgetown Lombardi is one of the centers currently conducting clinical trials of immunotherapy for patients with melanoma brain tumors.

“There are currently about 800 trials involving immunotherapy and immune therapy combinations to establish what drugs are effective against which types of cancer, which regimens work best, and how to reduce side effects, among other questions,” added Dr. Atkins.

In the phase II multicenter CHECKMATE 204 study, from which come the first efficacy data on melanoma patients with brain metastases treated with NIVO+IPI, Dr. Atkins and fellow researchers included melanoma patients with one or more measurable brain metastasis (0.5-3.0 cm) with no neurologic symptoms. Patients were treated with NIVO (1 mg/kg) plus IPI (3 mg/kg) every 3 weeks for four courses, and then NIVO (3 mg/kg) every 2 weeks until progression or toxicity.

They reported on data from 75 patients (median age: 59 years; median number of induction doses: 3). After a median follow-up of 6.3 months, the intracranial object response rate was 56% (95% CI: 44-68), and 19% had complete response.

“The response rate is more than each of the individual drugs’ response rates combined, so there seems to be a synergistic effect,” said Suthee Rapisuwon, MD, oncologist at Georgetown Lombardi.

Treatment-related grade 3 and 4 adverse events were seen in 48% of patients, of which 8% were neurologic (including headache and syncope). Only 4% of patients discontinued treatment due to treatment-related neurologic adverse events, and 1 patients died of immune-related myocarditis.

“Having these drugs available has changed my melanoma clinic from one with a lot of sad discussions going on to one that is more like a travel agency,” concluded Dr. Atkins. “So many patients are doing so well that they are doing things on their bucket lists.”