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).

Abstract

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.