Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Two-year overall survival (OS) rates from a randomized phase 2 trial evaluating the combination of nivolumab (NIVO) and ipilimumab (IPI) versus IPI in patients with advanced melanoma (MEL) (#253)

Michael A Postow 1 , Jason Chesney 2 , Anna C Pavlick 3 , Caroline Robert 4 , Kenneth Grossmann 5 , David McDermott 6 , Gerald Linette 7 , Nicolas Meyer 8 , Jeffrey Giguere 9 , Sanjiv S Agarwala 10 , Montaser Shaheen 11 , Marc S Ernstoff 12 , David R Minor 13 , April Salama 14 , Matthew H Taylor 15 , Patrick A Ott 16 , Joel Jiang 17 , Christine Horak 17 , Jedd D Wolchok 1 , Stephen Hodi 16
  1. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA
  2. J Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
  3. New York University, New York, NY , USA
  4. Cancer Institute Gustave Roussy, Villejuif, France
  5. Huntsman Cancer Institute, Salt Lake City, UT, USA
  6. Beth Israel Deaconess Medical Center, Boston, MA, USA
  7. Washington University, St Louis, USA
  8. Institut Universitaire du Cancer, Toulouse, France
  9. Greenville Health System, Greenville, SC, USA
  10. St Luke’s Cancer Center, Bethlehem, PA, USA
  11. University of New Mexico, Albuquerque, USA
  12. Cleveland Clinic, Cleveland, USA
  13. California Pacific Center for Melanoma Research , San Francisco, USA
  14. Duke University Medical Centre, Durham, NC, USA
  15. Oregon Health & Science University, Portland, OR, USA
  16. Dana-Farber Cancer Institute, Boston, MA, USA
  17. Bristol-Myers Squibb, Princeton, NJ, USA

Aims: NIVO and IPI combination therapy showed a significant improvement in objective response rate and progression-free survival (PFS) vs IPI alone in phase 2 and 3 studies in MEL patients. We report the first OS results evaluating NIVO+IPI in a randomized, controlled trial.

Methods: In this phase 2 trial (CheckMate 069), 142 patients were randomly assigned 2:1 (stratified by BRAF mutation status) to receive NIVO 1 mg/kg + IPI 3 mg/kg or IPI 3 mg/kg + placebo Q3W x 4, followed by NIVO 3 mg/kg or placebo, respectively, Q2W until progression or unacceptable toxicity. Primary endpoint was objective response rate among patients with BRAF wild-type MEL. Secondary endpoints included PFS in patients with BRAF wild-type tumors and safety. OS was an exploratory endpoint. Minimum follow-up was 2 years (database lock: February 2016).

Results:We randomized 95 patients to NIVO+IPI and 47 to IPI (72 and 37 patients with BRAF V600 wild-type tumors, respectively). OS rate in patients with BRAF wild-type tumors was 69% for NIVO+IPI vs 53% for IPI alone; median OS had not been reached in the NIVO+IPI group and was 24.8 months for the IPI group (hazard ratio 0.58, 95% CI 0.31-1.08). Two-year PFS rates were 54% for NIVO+IPI vs 11% for IPI alone; median PFS had not been reached in the NIVO+IPI group and was 4.4 months for the IPI group (hazard ratio 0.35, 95% CI 0.21-0.59, p<0.0001). Grade 3-4 treatment-related adverse events (AEs) were reported more frequently in NIVO+IPI patients (54%) vs IPI alone (20%) and led to discontinuation in 30% vs 9%, respectively.

Conclusions: The combination of first-line NIVO+IPI led to a numerically higher 2-year OS rate than first-line IPI alone in patients with MEL. There were no new safety signals with longer follow-up.