Overall survival at 4 years of follow-up in a phase 3 trial of nivolumab plus ipilimumab combination therapy in advanced melanoma (CheckMate 067)

Date 22 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Melanoma and other skin tumours
Topics Melanoma
Immunotherapy
Presenter F. Hodi
Authors F.S. Hodi1, V. Chiarion-Sileni2, R. Gonzalez3, J.J. Grob4, P. Rutkowski5, C..L. Cowey6, C. Lao7, D. Schadendorf8, J. Wagstaff9, R. Dummer10, P.F. Ferrucci11, M. Smylie12, A.G. Hill13, D. Hogg14, I. Marquez-Rodas15, J. Jiang16, J. Rizzo17, J. Larkin18, J. Wolchok19
  • 1Department Of Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2Melanoma And Esophageal Cancer Unit, Veneto Institute of Oncology IOV-IRCCS, Padua/IT
  • 3Division Of Medical Oncology, University of Colorado Cancer Center, Denver/US
  • 4Service De Dermatologie, Aix Marseille University, and APHM Hospital CHU Timone, Marseille/FR
  • 5Department Of Soft Tissue/bone Sarcoma And Melanoma, Maria Sklodowska-Curie Institute - Oncology Center, Warszawa/PL
  • 6Melanoma And Genitourinary Oncology Program, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas/US
  • 7Oncology, University of Michigan, Ann Arbor/US
  • 8Department Of Dermatology - Hautklinik, University of Essen, Essen, & German Cancer Consortium, Essen/DE
  • 9Medical Oncology, The College of Medicine, Swansea University, Swansea/GB
  • 10Dermatology, Universitäts Spital, Zurich/CH
  • 11Oncology, European Institute of Oncology, Milan/IT
  • 12Department Of Oncology, Cross Cancer Institute, Edmonton/CA
  • 13Medical Oncology, Tasman Oncology Research, Southport/AU
  • 14Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto/CA
  • 15Medical Oncology, General University Hospital Gregorio Marañón, Madrid/ES
  • 16Global Biometric Sciences, Bristol-Myers Squibb, Princeton/US
  • 17Oncology Clinical Development, Bristol-Myers Squibb, Princeton/US
  • 18Medicine, The Royal Marsden Hospital NHS Foundation Trust, 6JJ - London/GB
  • 19Melanoma & Immunotherapeutics, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York/US

Abstract

Background

Previous results from the CheckMate 067 study demonstrated a significant improvement in objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) with nivolumab plus ipilimumab (NIVO+IPI) and NIVO alone vs IPI alone in patients (pts) with advanced melanoma. Here, we report a 4-year update from CheckMate 067, representing the longest follow-up of a phase 3 study evaluating checkpoint inhibitor combination therapy.

Methods

Treatment-naive pts (N=945) were randomized 1:1:1 to (1) NIVO 1 mg/kg Q3W + IPI 3 mg/kg Q3W for 4 doses, followed by NIVO 3 mg/kg Q2W, (2) NIVO 3 mg/kg Q2W + placebo, or (3) IPI 3 mg/kg Q3W for 4 doses + placebo. Randomization was stratified by PD-L1 status, BRAF mutation status, and M stage. Pts were treated until progression or unacceptable toxicity. Co-primary endpoints were PFS and OS. Secondary endpoints included ORR and safety. While the study was not powered to compare the NIVO-containing groups, secondary objectives also included descriptive efficacy evaluations between NIVO+IPI and NIVO.

Results

At a minimum follow-up of 48 months, NIVO+IPI and NIVO continued to show a higher ORR and improved PFS and OS vs IPI (Table). Time from randomization to subsequent systemic therapy was longest with NIVO+IPI. Among pts alive at 4 years, 71% (113/159), 50% (69/138), and 39% (32/82) in the NIVO+IPI, NIVO, and IPI groups, respectively, were treatment free (off study treatment and had not received subsequent systemic therapy). No new safety signals were observed.

NIVO+IPI
(N=314)

NIVO
(N=316)

IPI
(N=315)

ORR, % (95% CI)

58 (53–64)

45 (39–50)

19 (15–24)

Median PFS, mo (95% CI)

11.5 (8.7–19.3)

6.9 (5.1–10.2)

2.9 (2.8–3.2)

4-year PFS rates, % (95% CI)

37 (31–42)

31 (25–36)

9 (6–13)

Median OS, mo (95% CI)

NR (38.2–NR)

36.9 (28.3–NR)

19.9 (16.9–24.6)

4-year OS rates, % (95% CI)

53 (47–58)

46 (41–52)

30 (25–35)

BRAF mutant

62 (52–71)

50 (39–59)

33 (24–42)

BRAF wild-type

49 (42–55)

45 (38–52)

28 (22–35)

PD-L1 <5%

52 (45–58)

45 (38–52)

28 (22–35)

PD-L1 ≥5%

61 (48–71)

54 (42–64)

36 (25–47)

Median time from randomization to subsequent systemic therapy, mo (95% CI)

NR

25.2 (16.0–43.2)

8.1 (6.5–8.7)

Conclusions

Long-term survival was achieved with NIVO+IPI and NIVO alone in pts with advanced melanoma. Descriptive analyses suggest higher survival rates with NIVO+IPI, and a higher proportion of pts treatment free, than with NIVO alone. First-line NIVO+IPI may reduce the need for subsequent therapy or prolong the time to subsequent therapy when needed.

Clinical trial identification

ClinicalTrials.gov, NCT01844505

Editorial Acknowledgement

Professional medical writing and editorial assistance were provided by Melissa Kirk, PhD, and Cara Hunsberger at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb.