Despite surgical advances and initial responses to chemo, OC has the highest mortality among gynecologic cancers, underscoring the need to improve long-term outcomes over standard platinum/taxane regimens. OC is a VEGF-driven tumor, susceptible to both the anti-angiogenic and immunomodulatory activities of bev. The immune response may also be enhanced by blocking the PD-L1/PD-1 and PD-L1/B7.1 pathways with atezo (anti–PD-L1), further potentiating anti-cancer T-cell activity. Atezo has shown safe and durable clinical benefit as a mono- and combinatorial therapy in human cancers, including OC. Here we present the first study in OC assessing dual immunomodulation with bev + atezo with standard chemo.
IMagyn050 (NCT03038100) will enroll ≈ 1300 newly diagnosed stage III-IV epithelial OC patients (pts) globally. Pts must have ECOG PS ≤ 2, evaluable tissue for PD-L1 testing (VENTANA SP142 assay) and will either have gross residual disease postoperatively (primary surgery group) or receive neoadjuvant (neo) therapy followed by surgery then adjuvant (adj) therapy (neo group). A concurrent phase (IV AUC6 carboplatin [Cb] + 175 mg/m2 paclitaxel [pac] + 15 mg/kg bev + 1200 mg atezo/PL × 6 cycles [C]) will be followed by maintenance bev + atezo/PL on 21-d C for a total of 22 C atezo/PL (Table), with pts treated until completion of maintenance therapy, toxicity or recurrence, whichever occurs first. The neo group will undergo neo therapy followed by interval surgery between C3-4 then adj therapy followed by maintenance bev + atezo/PL. Stratification factors are stage and/or residual disease, ECOG PS, PD-L1 status and treatment approach. Co-primary endpoints PFS and OS will be assessed in all and PD-L1−positive (≥ 1%) pts. Safety, efficacy, PROs and translational data will also be evaluated.Table:
|Treatment Groups (1:1 randomization)||Concurrent||Maintenance|
|Primary surgery||C1: Cb + pac + atezo/PL C2-6: Cb + pac + bev + atezo/PL||C7 onward: bev + atezo/PL|
|Neo||C1-2 and 5-6: Cb + pac + bev + atezo/PL C3-4: Cb + pac + atezo/PL||C7 onward: bev + atezo/PL|
Clinical trial identification
Legal entity responsible for the study
F. Hoffman-La Roche Ltd.
F. Hoffman-La Roche Ltd.
K.N. Moore: Serve on advisory boards for AstraZeneca, Advaxis, Clovis, Tesaro, Immunogen, Genentech/Roche, VBL Therapeutics; Serve on steering committees for Advaxis, Clovis And Immunogen. F. Wu: Roche employee. Y.G. Lin: Genentech‐Roche employee. S. Pignata: Honorarium by Roche. All other authors have declared no conflicts of interest.