Abstract 879TiP
Background
Cervical cancer is one of the most common and lethal cancers among women worldwide. Although pembrolizumab received accelerated FDA approval based upon overall response rate (ORR) and duration of response (DOR) for patients with recurrent/metastatic cervical cancer with tumors that express PD-L1, the ORR of 14.3% suggests that there remains a significant unmet need for patients with previously treated advanced cervical cancer unselected for PD-L1 expression. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. In a separate phase I trial (NCT02517398), bintrafusp alfa displayed clinical activity and a manageable safety profile in patients with heavily pretreated cervical cancer. We describe a single-arm phase II study that will assess the clinical activity and safety profile of bintrafusp alfa in platinum-experienced cervical cancer.
Trial design
This multicenter, global, phase II study will evaluate bintrafusp alfa monotherapy in patients with advanced unresectable and/or metastatic cervical cancer that progressed during or after platinum-based chemotherapy (CT) (NCT04246489). Prior platinum-containing CT may have been a systemic treatment for metastatic disease or in the adjuvant/neoadjuvant setting. Eligible patients must have an ECOG performance status of ≤1 and have not received prior checkpoint inhibitor therapy. Patients who have interstitial lung disease or a history of pneumonitis that required steroids will be excluded. Patients will receive bintrafusp alfa at the recommended phase II dose of 1200 mg Q2W. The primary endpoint is ORR according to RECIST 1.1 evaluated by an independent review committee; key secondary endpoints include DOR, durable response rate, safety, progression-free survival, overall survival, and pharmacokinetics. The clinical efficacy of bintrafusp alfa will be retrospectively evaluated according to PD-L1 expression. Estimated enrollment is 135 patients.
Clinical trial identification
NCT04246489.
Editorial acknowledgement
Medical writing support was provided by Spencer Hughes, PhD, of ClinicalThinking, Inc, Hamilton, NJ, USA, and funded by Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany and GlaxoSmithKline.
Disclosure
M.J. Birrer: Honoraria (self): Clovis; Honoraria (self): AstraZeneca; Honoraria (self): Roche/Genentech. K. Fujiwara: Honoraria (self), Research grant/Funding (institution): Chugai-Roche; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Nipponkayaku; Honoraria (self): Kyowa-Kirin; Honoraria (self), Research grant/Funding (institution): Zeria; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (institution): Genmab; Advisory/Consultancy: Nanocarrier; Research grant/Funding (institution): Regenerone. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche/Genentech; Non-remunerated activity/ies: GINECO; Non-remunerated activity/ies: ENGOT; Non-remunerated activity/ies: GCIG; Non-remunerated activity/ies: European Community; Non-remunerated activity/ies: ESMO; Non-remunerated activity/ies: ASCO; Non-remunerated activity/ies: ESGO; Non-remunerated activity/ies: IGSC; Non-remunerated activity/ies: Inca. Swiss, Italian, Belgium and German health authorities. J. Alexandre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: PharmaMar. A. Okamoto: Speaker Bureau/Expert testimony: AstraZeneca K.K.; Research grant/Funding (self): Kissei Pharmaceutical Co., Ltd; Research grant/Funding (self): Kaken Pharmaceutical Co., Ltd.; Research grant/Funding (self): Meiji Holdings Co., Ltd.; Research grant/Funding (self): Nippon Shinyaku Co., Ltd.; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd; Research grant/Funding (self): Taiho Pharmaceutical Co., Ltd.; Research grant/Funding (self): Daiichi Sankyo Co., Ltd.; Research grant/Funding (self): Tsumura & Co; Research grant/Funding (self): ASKA Pharmaceutical Co., Ltd. M.R. Mirza: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biocad; Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Advisory/Consultancy: Geneos; Advisory/Consultancy: Genmab; Advisory/Consultancy, Leadership role: Karyopharm Therapeutics; Advisory/Consultancy: Merck; Advisory/Consultancy: MSD; Advisory/Consultancy: Oncology Venture; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy, Leadership role: Sera Prognostics; Advisory/Consultancy: Sotio; Advisory/Consultancy, Research grant/Funding (institution): Tesaro-GSK; Advisory/Consultancy: ZaiLab; Leadership role: Boehringer Ingelheim. J.L. Gulley: Research grant/Funding (institution): Merck KGaA. G. Jehl: Full/Part-time employment: Merck KGaA. S. Ramage: Shareholder/Stockholder/Stock options: Merck KGaA; Full/Part-time employment: EMD Serono. L.S. Ojalvo: Licensing/Royalties, Full/Part-time employment: EMD Serono. S.M. Campos: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Tesaro (GSK); Honoraria (self): Eisai. All other authors have declared no conflicts of interest.