Startseite Kongressberichte & Archiv ESMO 2014, Madrid 26 - 30 September 2014 Melanoma H. Kluger, M. Sznol, M. Callahan, M. Postow et al.

H. Kluger, M. Sznol, M. Callahan, M. Postow et al.

Survival, response duration, and activity by BRAF mutation (MT) status in a phase 1 trial of nivolumab (anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL): 



In a phase 1 trial, concurrent therapy with nivolumab (N) + IPI (N + I) led to an objective response rate (ORR) of 40% and evidence of clinical activity in a further 25% of patients (pts). Tumor regression was generally rapid, with >80% reduction in tumor measurements in 31% of pts. We report updated survival, efficacy and clinical activity by BRAF MT status across all pt cohorts.


MEL pts (≤3 prior therapies) received concurrent N + I IV Q3W × 4 doses (Table; n = 53) followed by N Q3W × 4 doses. At wk 24, pts without progression by immune-related criteria (iRC) and no dose limiting toxicities could continue N + I Q12W × 8 doses. An additional 41 pts (cohort 8, last pt enrolled Nov 2013) were treated with N + I 1 + 3 mg/kg Q3W × 4 doses, followed by N 3 mg/kg Q2W (selected regimen for phase 2/3 trials). Tumor responses were evaluated by WHO and iRC.


Of the total 94 pts, 53% were stage M1c; 45% had prior systemic therapy. In the initially enrolled cohorts, ORR was 42% (22/53); median duration of response (DOR) not reached (NR); 9/53 (17%) demonstrated confirmed complete response. Fourteen of 22 pts (64%) with an OR had DOR ≥24 wks (range 24.7 + , 105.7+). Clinical activity was similar irrespective of BRAF MT status. Tumor reduction of ≥80% by wk 36 was observed in 22/53 pts (42%). One- and 2-yr OS rates were 85% and 79%, respectively. In cohort 8, ORR was 43% (17/40). For aggregate safety across cohorts, grade 3–4 treatment-related AEs occurred in 58/94 pts (62%); most common: increased lipase (15%), ALT (12%) and AST (11%).


Concurrent N + I demonstrated encouraging survival and a manageable safety profile using standard safety algorithms in advanced MEL pts. Responses were observed regardless of BRAF MT status and were durable in many pts. The preliminary analysis of cohort 8 confirms the activity of N + I observed in the initially enrolled concurrent cohorts.