Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (MBM; CheckMate 204)

Year: 2019

Hussein Tawbi¹,Peter Forsyth²,F. Stephen Hodi³,Christopher Lao⁴,Stergios Moschos⁵,Omid Hamid⁶,Michael B. Atkins⁷,Karl Lewis⁸,Reena P. Thomas⁹,John A. Glaspy¹⁰,Sekwon Jang¹¹,Alain Algazi¹²,Nikhil I. Khushalani²,Michael A. Postow¹³,Anna C. Pavlick¹⁴,Marc Ernstoff¹⁵,David A. Reardon³,Agnes Balogh¹⁶,Jasmine Rizzo¹⁶,Kim Margolin¹⁷

¹University of Texas MD Anderson Cancer Center, Houston, US,²Moffitt Cancer Center and Research Institute, Tampa, US,³Dana-Farber Cancer Institute, Boston, US,⁴University of Michigan, Ann Arbor, US,⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, US,⁶The Angeles Clinic and Research Institute, Los Angeles, US,⁷Georgetown Lombardi Comprehensive Cancer Center, Washington, US,⁸University of Colorado Comprehensive Cancer Center, Aurora, US,⁹Stanford University Hospital, Stanford, US,¹⁰Jonsson Comprehensive Cancer Center University of California, Los Angeles, US,¹¹Inova Schar Cancer Institute, Falls Church, US, Virginia Commonwealth University, Richmond, US,¹²University of California–San Francisco, San Francisco, US,¹³Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, US,¹⁴New York University Langone Medical Center, New York, US,¹⁵Roswell Park Cancer Institute, Buffalo, US,¹⁶Bristol-Myers Squibb, New York, US,¹⁷City of Hope, Duarte, US

Abstract

Background

We previously reported results of the phase 2 CheckMate 204 study (NCT02320058). Here, we provide updated data for patients with asymptomatic MBM and the first report of NIVO+IPI in patients with symptomatic MBM.

Method

Patients with ≥1 measurable, nonirradiated MBM 0.5–3.0 cm were enrolled into cohort A (asymptomatic: patients with no neurologic symptoms and no steroid treatment) or cohort B (symptomatic: patients with neurologic symptoms, regardless of steroid treatment). In both cohorts, patients received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x4, then NIVO 3 mg/kg Q2W until progression/toxicity. The primary endpoint was intracranial clinical benefit rate (CBR; CR + PR + SD ≥6 months). At the clinical cutoff date (May 1, 2018), all treated patients (101 in cohort A; 18 in cohort B) had been followed for ~6 months or longer.

Results

At a median follow-up of 20.6 months in cohort A, the CBR was 58% (95% CI, 48–68). In cohort B, patients received a median of 1 NIVO+IPI dose and 2/18 patients (11%) received all 4 doses; at a median follow-up of 5.2 months, intracranial ORR and CBR was 22% (95% CI, 6–48; 2 CRs, 2 PRs). Treatment-related grade 3/4 AEs occurred in 54% and 56% of patients in cohorts A and B, respectively (nervous system, 7% and 17%), with 1 treatment-related death in cohort A (immune-related myocarditis).

Conclusion

In patients with asymptomatic MBM, updated results showed a high rate of durable intracranial responses, supporting NIVO+IPI as a first-line treatment in this population. Intracranial antitumor activity was observed with NIVO+IPI in patients with symptomatic MBM, but further study is needed.

These results have been previously presented at the American Society for Clinical Oncology (ASCO) Annual Meeting, May 31–June 4, 2019, Chicago, IL, USA, and published in the conference proceedings (Abstract 9501).