BINTRAFUSP ALFA (M7824) is a bifunctional fusion protein that combines an anti-PD-L1 antibody and the extracellular domain of TGFβ receptor II (TGFβRII) as a TGFβ neutralizing 'trap', into a single molecule. The novel design of BINTRAFUSP ALFA (M7824), which neutralizes TGFβ and simultaneously inhibits the anti-PD-L1 pathway in the tumor microenvironment, may be more effective than agents targeting PD-L1 and TGFβ separately. In this trial, approximately 33 total patients are expected to be enrolled. The first phase of the study will be the safety lead in in 6 patients with advanced stage (stage III-IV) ovarian cancer undergoing neoadjuvant settings. Then 27 patients will be enrolled and randomized in 2:1 design to received standard chemotherapy with carboplatin/paclitaxel +/- M7824 respectively (N=18:9). Participants will be randomized so that there will be 24 PD-evaluable participants treated with standard of care chemotherapy plus BINTRAFUSP ALFA and 9 participants treated with standard of care chemotherapy at the end of the study. The control arm is strictly for comparison of the exploratory endpoints, although the primary and secondary endpoints will be presented for both arms, separately. The goal of including 9 patients in the control group is for comparison of the translational endpoint and not the clinical endpoint. For both regimens: M7824 (2400 mg flat dose iv on day 1 every 21 days) with chemotherapy including carboplatin AUC 5 and paclitaxel 175 mg/m2 on day 1 of 21-day cycle. Interval debulking surgery will be planned after 4 cycles. Chemotherapy will be planned for 6-8 cycles then maintenance M7824 will be continued for at 12 months.
In this study, the safety, tolerability, and anti-tumor activity of BINTRAFUSP ALFA in combination with chemotherapy will be assessed in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy.