2017 ASCO Annual Meeting!
Session: Developmental Therapeutics—Immunotherapy
Type: Poster Session
Time: Monday June 5, 8:00 AM to 11:30 AM
Location: Hall A
Augmentation of adoptive T-cell therapy for Merkel cell carcinoma with avelumab.
2017 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #139)
J Clin Oncol 35, 2017 (suppl; abstr 3044)
Author(s): Kelly Garneski Paulson, Maurizio Perdicchio, Rima Kulikauskas, Felecia Wagener, Candice Church, Kieu-Thu Bui, Natalie Vandeven, Hannah Thomas, Megan McAfee, Natalie Miller, Kevin M. Chin, Zhen Su, Philip D Greenberg, Upendra Parvathaneni, Shailender Bhatia, Paul Nghiem, Aude Chapuis; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington, Seattle, WA; EMD Serono, Inc., Billerica, MA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington Fred Hutchinson Cancer Center, Seattle, WA
Background: 80% of Merkel cell carcinomas (MCCs) are caused by Merkel cell polyomavirus (MCPyV) oncoproteins. Although absent in most cases, abundant MCPyV-specific CD8+ TIL are associated with good MCC outcomes, implying tumor susceptibility to immune attack. Indeed, anti-PD-1 axis blockade has a response rate of 32-56%. However, half of patients do not respond, suggesting a lack of adequate MCPyV-specific T cells and/or tumor evasion from MCC-related reduced HLA expression. We hypothesized the combination of adoptive transfer of MCPyV-specific T cells with HLA upregulation and PD1 axis blockade would be more effective than either approach alone. Methods: 8 adult patients with MCPyV-associated metastatic MCC without pre-existing immune deficiencies were enrolled. The safety and efficacy of ex vivo expanded MCPyV-specific T-cells plus HLA-upregulation (radiation or interferon) with (triple therapy) and without (double therapy) avelumab (mAb against PD-L1, dose 10 mg/kg IV q2weeks) were compared in 2 related phase I/II studies. Results: All 4 patients who received triple therapy (100%) are alive (median follow-up 10 months), and experienced objective responses (RECIST 1.1) with 3 of 4 sustained complete responses (CRs) at last follow-up (longest 13 mo). This compared favorably to outcomes among the 4 patients who received double therapy (3 with progression and 1 CR (25%) for 14 months before progression) and published data for avelumab monotherapy – response rate 32% and CR rate 9% in patients who had failed chemotherapy (Kaufman et al, Lancet Oncol, 2016). Grade 3-4 T cell-related adverse events were similar and anticipated in both groups, including transient lymphopenia (n = 7) and modest cytokine release syndrome lasting < 24 hours, manageable on the general ward (n = 4). No grade 3-4 toxicities were attributed to avelumab. Among patients receiving triple therapy, transferred T cells persisted, and peak frequencies correlated with rate of tumor regression. Conclusions: The combination of MCPyV-specific T cells, avelumab and HLA upregulation is safe and correlative studies suggest avelumab enhances the T cell responses to MCC. This strategy has potential for MCC treatment, and can be readily applied to other solid tumors. Clinical trial information: NCT01758458 and NCT02584829