Abstract
A multi-center phase II study of nivolumab +/- ipilimumab for patients with metastatic sarcoma (Alliance A091401)
Journal of clinical oncology, Vol.35(15_suppl), pp.11007-11007
05/20/2017
DOI: 10.1200/JCO.2017.35.15_suppl.11007
Abstract
11007
Background: Patients (pts) with metastatic sarcoma (SAR) have limited options. Nivolumab(N), a fully human anti-PD-1 mAb and ipilimumab (I), a humanized anti-CTLA-4 mAb, have favorable safety & efficacy in other tumors. Pembrolizumab demonstrated a response rate (RR) of 12% in SAR pts. We evaluated N, independently from N+I, in SAR pts. Methods: This open-label multi-center phase II study enrolled pts failing prior regimens. Randomized (non-comparative) pts received either N3 [N (3 mg/kg q2W)] or N3+I1 [N(3 mg/kg Q3W x4, then Q2W) & [I(1 mg/kg q3W x4)]. Treatment continued beyond progressive disease (PD) in 1
st
12 weeks. 5 confirmed responses in 38 evaluable pts yielded 90% power (0.05 1-sided alpha) to detect a 20% (vs 5%) confirmed RR. Other endpoints: adverse events (AEs), progression-free, overall survival (PFS, OS), and correlative studies including PD-L1 expression by IHC, mutational burden/neoantigen analysis, TCR clonality and TIL characterization. Results: 85 pts (43 - N3; 42 - N3+I1) were enrolled [mean age 54 yrs (21–81), 52% female). No significant differences in histological subtypes across cohorts: 36% LMS, 4% LPS, 10% UPS/MFH, 6% synovial, 5% bone, 5% Ewing’s, and 34% other. Pts were refractory to 1(20%), 2(22%), and ≥3 (58%) regimens. Grade 3-4 treatment related adverse events (TRAE) occurred in 7% (N3) and 14% (N3+I1) and 0 Gr 5 TRAEs. 8% of pts stopped due to AEs (2% N3, 14% N3+I1). 2/3 confirmed responses on N3, with 2 ongoing (range 1.1-3.2 months). 6/7 confirmed responses (2 complete) on N3+N1, with 5 ongoing (range 6-13 months). Responses occurred in 7 histologies. See Table for pt outcomes. Conclusions: N + I showed acceptable safety and encouraging antitumor activity with most responses ongoing across multiple SAR histologies, passing efficacy criteria. There was minimal activity observed with N alone. Increased TRAEs were observed in N3+I1. Correlative analyses ongoing. NCT02500797. Support: U10CA180821, U10CA180882, Conquer Cancer Foundation, BMS. Clinical trial information: NCT02500797. [Table: see text]
Details
- Title: Subtitle
- A multi-center phase II study of nivolumab +/- ipilimumab for patients with metastatic sarcoma (Alliance A091401)
- Creators
- Sandra P. D'Angelo - Memorial Sloan Kettering Cancer CenterMichelle R. Mahoney - Mayo ClinicBrian Andrew Van Tine - Washington University in St. LouisJames N Atkins - S.E. Cancer Control Consortium, Goldsboro, NC;Mohammed M. Milhem - University of IowaWilliam D. Tap - Memorial Sloan Kettering Cancer CenterCristina R. Antonescu - Memorial Sloan Kettering Cancer CenterLaura E. Horvath - Astellas Pharma US, Inc., Northbrook, ILGary K. Schwartz - Columbia University Irving Medical CenterHoward Streicher - National Institutes of Health
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.35(15_suppl), pp.11007-11007
- DOI
- 10.1200/JCO.2017.35.15_suppl.11007
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363316702771
Metrics
3 Record Views