In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. CT139-CT139
Abstract:
Background: This phase 1b trial evaluates the safety and antitumor efficacy of the combination of SD-101, a synthetic CpG-oligonucleotide that stimulates Toll-like receptor 9 (TLR9), and pembrolizumab in patients with recurrent Stage IIIC/IV malignant melanoma. Methods: Dose escalation of SD-101 used a modified 3+3 design. SD-101 was injected in a single tumor lesion (weekly x 4 doses then every 3 weeks x 7 doses over 6 months) at 1, 2, 4, or 8 mg and pembrolizumab was administered intravenously at 200 mg every 3 weeks up to 2 years. Tumor responses were assessed per investigator using RECIST v1.1 taking into account both injected and non-injected lesions. Results: Of the 22 patients, 9 were naïve to anti-PD-1/L1 therapy at baseline and 13 had progressive disease while receiving prior anti-PD-1/L1 therapy. Treatment was well tolerated with no Grade 3 or higher treatment-related AEs in longer term follow up. Among the 9 patients who were anti-PD-1/L1 naïve, best objective responses were CR: 2, PR: 5, PD: 1, not evaluated [NE]: 1. Median PFS, duration of response, and OS have not been reached. Estimated 12 month PFS was 88% and OS was 89%. After a median of 18 months of follow-up, 86% of responses were ongoing. One patient with a PR developed progressive disease after 20 months of treatment. Among patients who had received prior anti-PD-1/L1 therapy, best objective responses were PR: 2, SD: 5, PD: 5, NE: 1. One patient with stable disease and 1 patient with a PR continued on combination therapy without progression for at least 10.5 months. The other 10 patients developed progressive disease ranging from 1.5 to 8 months after enrollment. Percent change in tumor size from baseline in injected and non-injected lesions will also be presented. Conclusion: These early results suggest that combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially provide more clinical responses that are meaningfully durable than PD-1 blockade alone based on historical data. Citation Format: Antoni Ribas, Theresa Medina, Shivaani Kummar, Asim Amin, Joseph J. Drabick, Minal Barve, Gregory Daniels, Deborah L. Wong, Emmett V. Schmidt, Abraham C. Leung, Robert Janssen. Durability of responses to the combination of SD-101 and pembrolizumab in advanced metastatic melanoma: Results of a phase Ib, multicenter study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT139.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-CT139
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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