Abstract 45TiP
Background
Poly (ADP-ribose) polymerase (PARP) inhibitors alone and in combination with Bevacizumab have shown significant clinical benefit as maintenance therapy in women with newly diagnosed ovarian cancer (OC) regardless BRCA mutational status and in homologous-recombination deficiency (HRD)-positive patients, respectively. However, despite the remarkable improvements in the therapeutic algorithm of ovarian cancer disease over the years, several open questions remain: a) what is the best treatment in HRD-positive patients? b) what is the added value of bevacizumab in HRD positive tumors with respect to PARPi alone? c) what is the preferred treatment in HRD-negative tumors: PARPi or bevacizumab? MITO 25.1 aims to evaluate the best first line treatment regimen in the different molecular subgroups, HRD-positive and HRD-negative OC, evaluated with Foundation Medicine LOH test.
Trial Design
MITO 25.1 is a multicenter, randomized open-label, phase II study in which patients with high-grade serous or endometrioid advanced OC will be randomized in a 1:1 ratio according to a molecular driven treatment to receive: HRD-negative patients · ARM A: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 + Bev 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bev 15 mg/kg q 21 for 16 cycles · ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance HRD-positive patients · ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance · ARM C: Carboplatin AUC 5+ Paclitaxel 175 mg/m2 q 21 + Bev 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bev 15 mg/kg q 21 days for 16 cycles + Rucaparib 500 mg part BID q 28 for 24 cycles as maintenance The primary endpoint will be PFS. The secondary endpoints will be overall survival (OS), PFS2, adverse events according to CTCAE 5.0 and patient-reported outcome. Patients recruiting started in March 2021. To date, 136 of the 290 patients planned have been enrolled.
Clinical trial identification
NCT03462212.
Legal entity responsible for the study
D. Lorusso.
Funding
Clovis Oncology.
Disclosure
G. Scambia: Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Invited Speaker: Clovis Oncology. V. Salutari: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: Clovis-Oncology; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AstraZeneca. S. Pignata: Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Clovis-Oncology; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer. D. Lorusso: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Genmab; Other, Institutional, Member of the Board of Directors: GCIG. All other authors have declared no conflicts of interest.