Poster & Mini-oral COSA 2015 ASM

Clinical response, progression-free survival (PFS) and safety in patients (pts) with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI) versus IPI monotherapy in CheckMate 069 study (#163)

F Stephen Hodi 1 , Michael A Postow 2 3 , Jason Chesney 4 , Anna C Pavlik 5 , Caroline Robert 6 7 , Kenneth Grossman 8 , David McDermott 9 , Gerald Linette 10 , Nicolas Meyer 11 , Jeffrey K Giguere 12 13 , Sanjiv S Agarwala 14 , Montaser Shaheen 15 , Marc S Ernstoff 16 , David Minor 17 , April K Salama 18 , Matthew Taylor 19 , Patrick A Ott 1 , Christine Horak 20 , Paul Gagnier 21 , Jedd D Wolchok 2
  1. Dana-Farber Cancer Institute, Boston, MA, USA
  2. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA
  3. Weill Cornell Medical College, New York, NY, USA
  4. J Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
  5. New York University, Perlmutter Cancer Center , New York, NY, USA
  6. Cancer Institute Gustave Roussy, Villejuif, France
  7. Paris-Sud University, Villejuif-Paris-Sud, France
  8. Huntsman Cancer Institute, Salt Lake City, UT, USA
  9. Beth Israel Deaconess Medical Center, Boston, MA, USA
  10. Washington University, St Louis, MO, USA
  11. Institut Universitaire du Cancer, Toulouse, France
  12. Greenville Health System, Greenville, SC, USA
  13. Greenville Health System, Greenville, SC, USA
  14. St Luke’s Cancer Center, Bethlehem, PA, USA
  15. University of New Mexico, New Mexico, NM, USA
  16. Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA
  17. California Pacific Center for Melanoma Research, San Francisco, CA, USA
  18. Duke University Medical Centre, Durham, NC, USA
  19. Oregon Health & Science University, Portland, OR, USA
  20. Bristol-Myers Squibb, Princeton, NJ, USA
  21. Bristol-Myers Squibb, Wallingford, CT, USA

Aims: Combined blockade of T-cell checkpoints by NIVO and IPI demonstrated a high objective response rate (ORR), promising overall survival and a manageable safety profile in pts with advanced MEL. We report efficacy and safety of NIVO + IPI vs IPI alone in treatment-naïve pts with advanced MEL in a phase 2 study.

Methods: Pts (N=142) with metastatic or unresectable MEL were randomized 2:1 to receive IPI 3 mg/kg combined with either NIVO 1 mg/kg or placebo Q3W × 4, followed by NIVO 3 mg/kg or placebo Q2W until disease progression or unacceptable toxicity. The primary endpoint was ORR in BRAF wild-type (WT) pts. Secondary and exploratory objectives included PFS in BRAF WT pts, ORR and PFS in BRAF V600 mutation-positive (MT) pts, and safety.

Results: In BRAF WT pts (n=109), ORR was 61% (44/72) for NIVO + IPI; 11% (4/37) for IPI alone (P<0.0001); complete responses were reported in 16 (22%) and 0 pts, respectively; median PFS was not reached and 4.4 months, respectively (P=0.0006). Higher ORR was observed for NIVO + IPI vs IPI in poor prognostic pt subgroups: elevated baseline lactate dehydrogenase (53% vs 0%); M1c stage disease (65% vs 25%). Similar ORR and PFS were observed in 33 BRAF MT pts. Grade 3–4 drug-related adverse events were reported in 54% of pts receiving NIVO + IPI and 24% for IPI alone, the majority of which resolved with the use of immune modulatory medication.

Conclusions: NIVO + IPI significantly improved ORR and PFS compared with IPI alone, had a safety profile generally managed with established safety guidelines, and provided a favorable risk-benefit ratio in treatment-naïve pts with advanced MEL.

Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2015 ASCO Annual Meeting. All rights reserved.