Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Updated results from a phase 3 trial of nivolumab (NIVO) combined with ipilimumab (IPI) in treatment-naive patients with advanced melanoma (MEL) (CheckMate 067) (#244)

Jedd D Wolchok 1 , Vanna Chiarion-Sileni 2 , Rene Gonzalez 3 , Piotr Rutkowski 4 , Jean-Jacques Grob 5 , C.Lance Cowey 6 , Christopher D Lao 7 , Dirk Schadendorf 8 , Pier F Ferrucci 9 , Michael Smylie 10 , Reinhard Dummer 11 , Andrew Hill 12 , John Haanen 13 , Michele Maio 14 , Grant McArthur 15 , Dana Walker 16 , Joel Jiang 16 , Christine Horak 16 , James Larkin 17 , Stephen Hodi 18
  1. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA
  2. Oncology Institute of Veneto IRCCS, Padua, Italy
  3. University of Colorado Cancer Center, Denver, CO, USA
  4. Centrum Onkologii - Instytut Im. Marii Sklodowskiej-Curie, Warsaw, Poland
  5. Hôpital de la Timone, Marseille, France
  6. Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA
  7. University of Michigan, Ann Arbor, MI, USA
  8. Department of Dermatology, University of Essen, Essen, Germany
  9. European Institute of Oncology , Milan, Italy
  10. Cross Cancer Institute, Alberta, Canada
  11. Universitäts Spital, Zurich, Switzerland
  12. Tasman Oncology Research, Southport Gold Coast, Queensland, Australia
  13. The Netherlands Cancer Institute, Amsterdam, Netherlands
  14. University Hospital of Siena, Siena, Italy
  15. Peter MacCallum Cancer Center, Victoria, Australia
  16. Bristol-Myers Squibb, Princeton, NJ, USA
  17. Royal Marsden Hospital, London, United Kingdom
  18. Dana-Farber Cancer Institute, Boston, MA, USA

Aims: In CheckMate 067, NIVO+IPI significantly improved progression-free survival (PFS) and objective response rate (ORR) vs IPI alone in MEL patients. We report updated efficacy and safety results from this study.

Methods: Patients (N=945) were randomized 1:1:1 to NIVO 1 mg/kg Q3W + IPI 3 mg/kg Q3W x 4 (followed by NIVO 3 mg/kg Q2W), NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W x 4 + placebo, until progression or unacceptable toxicity. Patients were stratified by PD-L1 status, BRAF mutation status, and M-stage. Co-primary endpoints were PFS and overall survival (data remain immature). Secondary endpoints included efficacy by PD-L1 status and safety.

Results: At ≥18 months of follow-up, median PFS continued to be significantly longer for NIVO+IPI (11.5 months; 95% confidence interval [CI], 8.9-22.2) and NIVO (6.9 months; 95% CI, 4.3-9.5) vs IPI (2.9 months; 95% CI, 2.8-3.4) (P<0.001), and was numerically longer for NIVO+IPI vs NIVO alone (0.76; 95% CI, 0.60-0.92). Median duration of response in 57.6% NIVO+IPI responders has not been reached, and was 22.3 and 14.4 months in 43.7% NIVO and 19.0% IPI responders, respectively. Median PFS was also numerically longer with NIVO+IPI vs NIVO or IPI regardless of PD-L1 expression. For NIVO+IPI, NIVO, and IPI groups, median PFS was 15.5, 5.6, and 4.0 months in patients with a BRAF mutation and was 11.3, 7.1, and 2.8 months in patients with wild-type BRAF, respectively. The frequency and types of drug-related grade 3/4 AEs were consistent with earlier reports (NIVO+IPI, 56.5%; NIVO, 19.8%; IPI, 27.0%). NIVO+IPI and NIVO continue to demonstrate superior clinical activity vs IPI.

Conclusions: NIVO+IPI resulted in numerically greater PFS and ORR than NIVO alone, including in patients with a BRAF mutation.