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

LBA9003^ Background: We report updated survival and clinical activity in initially enrolled cohorts and activity by BRAF MT status in a phase I trial of concurrent and sequenced NIVO + IPI. Methods: MEL pts (n=53, enrolled 2009-2012, data analysis Dec 2013) with ≤3 prior therapies received IV concurrent NIVO + IPI, Q3Wk × 4 doses, followed by NIVO Q3Wk × 4. At wk 24, NIVO + IPI continued Q12Wk × 8 in pts with disease control and no DLT. Tumor responses were evaluated by WHO and immune-related criteria. Results: Pt characteristics included stage M1c: 55% and prior systemic therapy: 40%. Across doses, 1- and 2-y OS rates were 82% and 75%. Clinical activity was similar to previous reports except CRs rose to 9/53 (17%). Pts with/without tumor BRAF MT (n=36) had similar activity (Table). By wk 36, 42% demonstrated ≥80% tumor reduction. Median duration of response (DOR) was not reached (NR). Of 22 pts with objective response, 14 (64%) had DOR ≥24 wk (range: 25+, 106+). Treatment-related adverse events were as reported previously: grade 3-4, 53% of pts; most common: ↑ lipase and AST (13% ea). Data for sequenced cohorts are shown (Table). Conclusions: Concurrent NIVO + IPI therapy showed encouraging survival and a manageable safety profile in advanced MEL pts. Responses were observed regardless of BRAF MT status and were durable in the majority of pts. Forty additional pts were enrolled (last pt: Nov 2013) on a cohort of NIVO 1 mg/kg + IPI 3 mg/kg Q3Wk × 4 doses, followed by NIVO 3mg/kg Q2Wk (the selected regimen for phase II/III trials). Clinical trial information: NCT01024231. NIVO (mg/kg) + IPI (mg/kg) n 1-Y OS rate, % pts at risk Median OS, mo ACAR, % ACAR by BRAF MT status, * % n Pos Neg Unk 0. 3 + 3 14 56 7 14. 8 57 50 4 67 3 57 7 1 + 3 17 94 13 NR 65 50 2 50 6 78 9 3 + 1 16 89 3 NR 81 67 3 85 13 – 0 3 + 3 6 100 5 NR 83 100 1 75 4 100 1 Concurrent 53 82 28 39. 7 70 60 10 73 26 71 17 Sequenced† 32 Insufficient followup 13. 0 44 44 9 47 15 38 8 n: no. response-evaluable pts. ACAR: aggregate clinical activity rate = CR+PR+uCR+uPR+irCR+irPR+SD ≥24 wk+ irSD ≥24 wk. *Retrospective analysis. †Pts began NIVO Q2Wk × 48 doses within 4-12 wk after last IPI dose.