Abstract 3610
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 | NIVO | IPI |
| 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.