752P - Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic squamous cell cervix carcinoma: Subgroup analysis of the PEVOsq basket trial

Background

Adding pembrolizumab (P) to standard first-line chemotherapy +/- bevacizumab in cervical cancer significantly improved survival. However, more than half of patients (pts) will present a relapse before 12 months. Virtually all cases of cervical cancer are attributable to HPV infection. Preclinical evidence suggests that histone deacetylase inhibitor vorinostat (V), might be active in both HPV 16 and HPV 18 related infections and might improve immunotherapy efficacy giving the rationale for combining P + V in cervical cancer.

Methods

PEVOsq is an open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of P+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. 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, 25 were included in the cervix cohort. Median age was 52 years [range(r): 31-75]. The median number of prior lines of therapies was 1 [r: 0-3]. Among 23 pts evaluable for activity criteria, ORR was 39.1% [95%CI: 19.7-61.5]. Median PFS was 4.2 months [95%CI: 2.3-8.2] and OS was 10.3 months [95%CI: 5.7-NR]. DOR was 15.2 months [95%CI 1.4-NR]. Grade 3/4 Treatment related AE were frequent (44%). Seventeen pts (68%) had at least one treatment interruption and/or dose reduction due to toxicity for V including hematotoxicity, gastrointestinal disorders, asthenia, and creatinine increase. Six pts (24%) had at least one administration delayed due to toxicity for P. Median dose intensity for V was 271.4 mg/j [r: 108.7 – 400]. Dose intensity for V was 271.1mg/d [r: 108.7-400.0] and 260.5mg/d [r: 199.4-400.0] in pts with ORR and others (SD/PD), respectively. Results according to PDL1, MSI, TMB and HPV will be presented at the meeting.

Conclusions

Combining P and V in cervical cancer was effective even though dose adaptations for V were frequent.

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.