126008-144

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).

Subcategory: 
Category: 
Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
LBA9003^
Citation: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA9003^)
Author(s): 
Mario Sznol, Harriet M. Kluger, Margaret K. Callahan, Michael Andrew Postow, Ruth Ann Gordon, Neil Howard Segal, Naiyer A. Rizvi, Alexander M. Lesokhin, Michael B. Atkins, John M. Kirkwood, Matthew M. Burke, Amanda L. Ralabate, Angel L. Rivera, Stephanie Anne Kronenberg, Blessing Agunwamba, William Feely, Quan Hong, Suba Krishnan, Ashok Kumar Gupta, Jedd D. Wolchok; Yale Cancer Center, New Haven, CT; Memorial Sloan Kettering Cancer Center, New York, NY; Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; University of Pittsburgh Medical Center, Pittsburgh, PA; Bristol-Myers Squibb, Princeton, NJ

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

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.