Abstract 1989
Background
While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in patients with metastatic uveal melanoma. Reports of treatment with immune checkpoint inhibitors in monotherapy have been disappointing. There is preclinical evidence that the effect of immunotherapy may be augmented by epigenetic therapy through mechanisms including enhanced expression of HLA class I and cancer antigens, and suppression of myeloid suppressor cells.
Methods
We performed a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD-1 inhibitor pembrolizumab and the HDAC inhibitor entinostat in 29 adult patients with metastatic uveal melanoma. Eligible patients had histologically confirmed metastatic uveal melanoma, ECOG performance status 0–1, and measurable disease as per RECIST 1.1. Patients received pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Primary endpoint was objective response rate (ORR). Secondary endpoints include clinical benefit rate (CBR; CR, PR or SD) at 18 weeks, overall survival (OS), and safety assessed by adverse events (AE).
Results
At the data cut off of June 21, 2019, 29 patients had been enrolled and received at least one dose of treatment with a median follow up of 7.7 months. Ninety per cent had liver metastases and 59% had received previous treatment for metastatic disease. A partial response (PR) was observed in 3 patients resulting in an ORR of 10%. Nine patients (31%) had a best overall response of stable disease (SD). Clinical benefit at week 18 was observed in 7 out of 29 patients (24%). Median OS was 11.5 months. Twenty-eight patients (97%) experienced treatment related AEs, and grade 3-4 AEs were reported in 18 patients (62%). There were no treatment related deaths.
Conclusions
The PEMDAC study has demonstrated that combined HDAC- and PD-1-inhibition can result in clinical efficacy in metastatic uveal melanoma with manageable toxicities. The obtained data warrant further investigation to address clinical and immunological characteristics of patients achieving clinical benefit.
Clinical trial identification
NCT02697630 (Registered 3 March 2016). EudraCT: 2016-002114-50.
Editorial acknowledgement
Legal entity responsible for the study
Sahlgrenska University Hospital, Västra Götaland Region.
Funding
Syndax Pharmaceuticals and Merck & Co. Inc.
Disclosure
R. Olofsson Bagge: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). G. Ullenhag: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). I. Ljuslinder: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). M. Levin: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). U. Stierner: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). L. Ny: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). All other authors have declared no conflicts of interest.
Resources from the same session
Poster Discussion – Melanoma and other skin tumours - Invited Discussant 1312PD and one LBA TBC
Presenter: Paolo Ascierto
Session: Poster Discussion – Melanoma and other skin tumours
Resources:
Slides
Webcast
Poster Discussion – Melanoma and other skin tumours - Invited Discussant 3 LBAs TBC
Presenter: Ana Arance
Session: Poster Discussion – Melanoma and other skin tumours
Resources:
Slides
Webcast
Poster Discussion – Melanoma and other skin tumours - Invited Discussant 1313PD and one LBA TBC
Presenter: Piotr Rutkowski
Session: Poster Discussion – Melanoma and other skin tumours
Resources:
Slides
Webcast
Poster Discussion – Melanoma and other skin tumours - Invited Discussant 1314PD, 1315PD, and 1316PD
Presenter: Salvador Martin Algarra
Session: Poster Discussion – Melanoma and other skin tumours
Resources:
Slides
Webcast