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Background: Immunotherapy is an effective treatment for patients with metastatic melanoma. However, immune checkpoint inhibitors (ICI) often induce immune-related adverse events and despite high response rates many patients still progress. Nivolumab combined with a peptide vaccine designed to engage and activate IDO- and PD-L1 specific T cells is a promising approach for treating advanced melanoma without inducing the amount of toxicity observed in combination ICI treatment. Methods: In an investigator-initiated phase I/II study (ClinicalTrials.gov: NCT03047928) anti-PD-1 naive stage IV melanoma patients received a maximum of 15 IDO/PD-L1 peptide vaccine [1] doses SC (6x q2w followed by 9x q4w). Nivolumab (3 mg/kg) was administered every second week (q2w) for a maximum of two years. Clinical efficacy, toxicity, and survival data were evaluated [2]. Responses were assessed according to RECIST 1.1. Results: Here we present the updated efficacy data and subgroup analyses. As of data cut-off, December 1, 2021, all 30 patients were evaluated after completing the IDO/PD-L1 vaccination schedule in combination with nivolumab. The overall response rate (ORR) was 80% (n=24) with 46.7% (n=14) of patients obtaining complete responses (CR). After a median follow-up of 2.7 years, the median progression free survival (mPFS) was 25.3 months and median overall survival (mOS) was not reached. The three-year survival probability is 73%. A subgroup analysis showed that in PD-L1+ patients, RR was 94.1% with mPFS: 30.9 months. In PD-L1- patients RR was 61.5%, with mPFS: 7.2 months. Furthermore, in poor prognosis patients with elevated baseline LDH-levels, the RR was 81.8%, with mPFS: 30.9 months. In patients with non-elevated baseline LDH-levels, the RR was 78.9%, with mPFS: 19.3 months. Finally, in patients classified as M1c at baseline RR was 88.2%, with mPFS: 25.6 months, and patients classified as M1a or M1b at baseline had RR: 69.2% with mPFS: 14.8 months. The immune-related adverse events were comparable to patients receiving Nivolumab monotherapy and no additional toxicity was observed in poor prognosis patients. Conclusion: The combination of an PD-L1/IDO peptide vaccine and nivolumab is an effective treatment for patients with metastatic melanoma. The clinical efficacy- and survival data are very encouraging with ORR of 80% of which 46.7% were CR. After a median follow-up of 32 months, the mPFS was 25.3 months which is twice the expected for patients receiving standard treatment of care. Importantly, we report that patients with unfavorable prognostic baseline characteristics at inclusion obtain impressive response rates and durable responses without additional toxicity. 1 IO Biotech (www.iobiotech.com) has licensed the patent of the vaccine IO102/IO103 T-win® 2Results are reported in Nature Medicine, December, 2021 Citation Format: Julie W. Kjeldsen, Cathrine L. Lorentzen, Evelina Martinenaite, Eva Ellebaek, Marco Donia, Eva Ehrnrooth, Mads H. Andersen, Inge Marie Svane. High clinical efficacy in poor prognosis patients with metastatic melanoma treated with an IDO/PD-L1 peptide vaccine in combination with nivolumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT535. |
