557MO - Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic anal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial

Background

No standard therapies beyond first line are established for advanced squamous cell anal carcinoma (SCAC). Although PD-1 blockade demonstrated activity in patients (pts) with advanced SCAC, response rate is modest. Preclinical data suggests that vorinostat (V), an HDAC inhibitor, might improve immunotherapy efficacy by modulating the epigenome.

Methods

PEVOsq is an open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of pembrolizumab (P) in combination with V in pts with recurrent and/or metastatic squamous carcinomas. Pts had to be PD1/PD-L1 antagonist-naïve with no restriction in terms of prior lines of treatments. P dose was 200 mg Q3W IV, and V 400 mg QD PO. Sample size was determined using an A’Hern design with the following hypotheses (alpha=5%, power=90%, p0=15%, p1=40%). Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and duration of response (DOR).

Results

Among 112 included pts, 29pts with SCAC were evaluable for safety and efficacy. Median age was 63 years old [range: 49-84], 23 were female and the median number of prior lines of therapies was 2 [range: 0-4]. Nine pts (31.0%) had an objective response [95%CI: 17.2; 47.9] and median DOR was not reached [95%CI: 5.6-NR]. Median PFS and OS were 5.8 [95%CI: 2.7-11.0] and 18.8 months [12.8-NR] respectively. Among the 22 pts with p16 evaluated, all were positive. Eighteen (62.1%) pts developed G3/4 treatment related adverse events. P and V were stopped for toxicity in 13.0% and 44.4% of pts, respectively. 79.3% of pts had a dose-reduced of V for toxicity including hematotoxicity, gastrointestinal disorders, asthenia and creatinine increase. Results according to PDL1, MSI, TMB and HPV will be presented at the meeting.

Conclusions

PEVOsq study met its primary endpoint, documenting promising anti-tumoral activity of the association of P+V in heavily pretreated SCAC pts. However, the high rate of toxicities requires a special attention in future trials.

Clinical trial identification

NCT04357873, EudraCT 2019-003839-33.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

ERAPerMED ANR Fondation ARC.

Disclosure

All authors have declared no conflicts of interest.