Abstract 817TiP
Background
NP137, a first-in-class humanized monoclonal antibody targeting netrin-1, by restoring apoptosis in tumor cells and by reversing tumoral epithelial to mesenchymal transition, able to promote response to chemotherapies and immunotherapies. NP137 has previously demonstrated in phase I monotherapy study a manageable safety profile and preliminary activity as a single agent in pts with gynecological carcinoma (NCT02977195).
Trial design
This multicenter, open label, multi-arms, randomized, Phase I/II investigates safety and clinical activity of NP137 combined with pembrolizumab and/or chemotherapy in in endometrial and cervix carcinoma. Eligible pts progressing/relapsing after 1 to 3 prior chemotherapy (CT) lines are randomly assigned (ratio 1:1:1:1) to one of the following arms: carboplatin + paclitaxel (standard regimen, Q3W, IV) alone; carboplatin + paclitaxel with NP137 (14 mg/kg, Q3W, IV); NP137 combined with Pembrolizumab (200 mg, Q3W, IV) and NP137 combined with Pembrolizumab and Carboplatin + Paclitaxel. Randomization is stratified according to the number of prior chemotherapy lines and the MSI/MSS status. A maximum of 30 pts will be enrolled in each arm for both tumor type cohort for a total sample size of 240 pts. A safety run is planned on first 6 to 12 pts in each arm to assess the safety of the therapeutic combinations. Primary endpoint is defined as the 3-month ORR assessed by an independent central review as per RECIST 1.1. An adaptive Bayesian approach will allow to quickly stop treatment cohorts without evidence of efficacy and/or select promising treatment cohorts. Secondary endpoints include Disease Control Rate, Duration of Response, Progression Free Survival, Overall Survival, pharmacokinetics and translational researches for biomarkers of efficacy and resistance. Enrollment started in December 2020. The triple combination arm will be opened once safety of double combinations is confirmed.
Clinical trial identification
NCT04652076.
Editorial acknowledgement
This study is granted by French National Research Agency (ANR-18-RHUS-0009) and sponsored by NETRIS Pharma in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and ARCAGY-GINECO group (The trial will be conducted with investigators of the ARCAGY-GINECO group. A list of the GYNET principal investigators is available on https://rhu-depgyn.com)
Legal entity responsible for the study
Netris Pharma.
Funding
Has not received any funding.
Disclosure
I. Ray-Coquard: Non-Financial Interests, Institutional, Advisory Board: Netris Pharma. P. Mehlen: Financial Interests, Personal and Institutional, Member of the Board of Directors: Netris Pharma. A. Bernet: Non-Financial Interests, Personal and Institutional, Other: Netris Pharma. F. le bras: Financial Interests, Institutional, Officer: Netris Pharma. C. Mastier: Financial Interests, Institutional, Research Grant: Netris Pharma. B. Ducarouge: Financial Interests, Institutional, Full or part-time Employment: Netris Pharma. D. Perol: Financial Interests, Institutional, Funding: Netris Pharma. J. Blay: Non-Financial Interests, Institutional, Advisory Board: Netris Pharma. All other authors have declared no conflicts of interest.