DUO-E/GOG-3041/ENGOT-EN10: a randomized phase III trial of first-line carboplatin (carb) and paclitaxel (pac) in combination with durvalumab (durva), followed by maintenance durva with or without olaparib (ola), in patients (pts) with newly diagnosed (nd) advanced or recurrent endometrial cancer (EC).
Shannon N. Westin, Kathleen N. Moore, Els Van Nieuwenhuysen, Amit M. Oza, Linda Mileshkin, Aikou Okamoto, Akiko Suzuki, Kassondra Meyer, Laura Barker, Joon Haeng Rhee, Ignace Vergote
Abstract
TPS6108 Background: There is a high unmet need for advances in EC treatment that provide progression-free survival (PFS) and overall survival (OS) benefits. EC tumors are sensitive to carb/pac (Pectasides et al. Gynecol Oncol 2008). Maintenance therapy with the poly(ADP-ribose) polymerase inhibitor (PARPi) ola (with or without bevacizumab) led to significant PFS benefits in advanced ovarian cancer pts with either nd (SOLO1, Moore et al. NEJM 2018; PAOLA-1, Ray-Coquard et al. NEJM 2019) or recurrent (SOLO2, Pujade-Lauraine et al. Lancet Oncol 2017; Study 19, Friedlander et al. Br J Cancer 2018) platinum-sensitive disease, regardless of BRCA mutation status (PAOLA-1; Study 19), and in BRCA-mutated metastatic pancreatic cancer pts (POLO, Golan et al. NEJM 2019). Molecular features of EC could predict sensitivity to PARPi (de Jonge et al. Clin Cancer Res 2019; Auguste et al. Mod Pathol 2018). PARPi has been shown to prime the immune microenvironment in a preclinical BRCA1 mutant ovarian model (Higuchi et al. Cancer Immunol Res 2015). Clinical trials have demonstrated antitumor activity of the anti-programmed cell death ligand-1 (anti-PD-L1) blocker durva (Antill et al. J Clin Oncol 2019) and anti-programmed cell death-1 (anti-PD-1) antibody therapies (Makker et al. ESMO 2019; Oaknin et al. SGO 2019) in EC pts. The DUO-E trial (EUDRACT 2019-004112-60, D9311C00001, NCT04269200) will investigate whether the addition of durva to carb/pac, followed by durva (with or without ola) maintenance treatment, improves PFS in pts with nd advanced or recurrent EC. Methods: Eligible pts for this multicenter, double-blind, Phase III trial must have nd Stage III/IV or recurrent EC and be naïve to first-line chemotherapy. Pts will be randomized (1:1:1; n=~233 per arm) to: arm A) carb/pac + placebo (pbo) (q3w for six cycles) followed by pbo maintenance treatment; arm B) carb/pac + durva (1120 mg; q3w for six cycles) followed by maintenance treatment with durva (1500 mg q4w) + pbo (tablets bid); or arm C) carb/pac + durva (1120 mg; q3w for six cycles) followed by maintenance treatment with durva (1500 mg q4w) + ola (300 mg bid tablets). Pts received maintenance treatment until disease progression. Primary endpoint: investigator-assessed PFS (RECIST 1.1) of arm B vs. arm A. Key secondary endpoints: PFS of arm C vs. arm A; OS of arm B vs. arm A, and of arm C vs. arm A. Enrollment began in Q1 2020. Clinical trial information: 2019-004112-60.