521MO Efficacy of pembrolizumab monotherapy (PM) for advanced clear cell gynaecological cancer (CCGC): Phase II PEACOCC trial

Abstract

Advanced CCGC has poor prognosis with 2nd line objective response rates (ORR) to standard chemotherapy ranging from 0-8%. As PD-L1 expression, PD-1+ tumour infiltrating lymphocytes, pro-inflammatory cytokine signalling, high tumour mutational burden and preliminary clinical activity with PD-1 inhibitors are described in CCGC, we investigated PM for advanced CCGC. PEACOCC is a Phase II, multicentre, single arm, academic, UK trial in patients (pts) with advanced CCGC who had ≥1 prior line of chemotherapy with progression (PD) at study entry. Pembrolizumab 200mg iv q21 days was given until PD (RECIST v1.1), unacceptable adverse event (AE), 2 years (y) PM reached, patient or clinician decision. The primary endpoint was progression-free survival (PFS) rate at 12 weeks (w) (H0≤15%; H1≥33%; 5% 1-sided a; 90% power). Secondary endpoints included ORR, duration of response (DOR), PFS, overall survival (OS) and safety. From 4/3/19–20/10/21 49pts were enrolled, 48 evaluable. Median age 58.5y (32–77y), ECOG 0/1 54.2%/45.8%, 85.4% ovarian CCGC. Median prior lines systemic therapy 2 (1–6); 19pts (39.6%) had received anti-angiogenic therapy. 42pts completed median 4 cycles PM (1–25), 6pts (12.5%) continue PM. 16.7% pts had Grade (G)3 treatment-related AE (TRAE) of hyperthyroidism (n=2), acute kidney injury (AKI), raised alanine aminotransferase, raised alkaline phosphatase, anaemia, encephalitis and diabetic ketoacidosis (DKA). There were no G4 or G5 TRAE. 3pts (6.3%) discontinued PM due to TRAEs. The PFS rate at 12w was 43.8% (90%CI:31.5-56.6) exceeding the pre-stated lower bound of 15%. Best ORR was 25.0% (90%CI:15.1-37.3) [1 complete, 11 partial], with 1y DOR rate 47.7% (95%CI:14.1-75.6). After a median follow-up of 2.1y, median PFS was 12.2w (95%CI:5.9-32.9) and median OS 71.0w (95%CI:29.1-137.6). The PEACOCC trial indicates that PM is a highly effective therapy in heavily pre-treated pts with advanced CCGC: 43.8% pts were alive and progression-free at 12w. Furthermore, clinical outcomes were durable with limited toxicity. These promising results justify consideration of pembrolizumab monotherapy as a new standard-of-care for advanced CCGC.