NCT04652076

GYNecological Cancers Treated with NETrin MAbs in Combination with Chemotherapy and /or Pembrolizumab

A Randomized, Multicenter, Open Label, Phase I/II Study to Evaluate the Safety, Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination with Carboplatin Plus Paclitaxel And/or Pembrolizumab in Patients with Locally Advanced/metastatic Endometrial Carcinoma or Cervix Carcinoma Progressing/relapsing After At Least One Prior Systemic Chemotherapy.

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: NETRIS Pharma · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with pembrolizumab and/or chemotherapies in patients with advanced/metastatic gynecological cancers (2 types: endometrial carcinoma and cervix carcinoma).

Detailed description

The prognosis of patients with locally advanced/metastatic uterine (endometrial or cervical) cancer progressing/relapsing after at least one prior systemic treatment remains poor. The development of new innovative anti-tumor drug candidates as single agent or in combination with chemotherapy or check point inhibitors is needed. NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. By blocking Netrin-1, NP137 is capable of restoring apoptosis in tumor cells in vitro and in vivo, leading to therapeutic activity in various animal cancer models. Dependence receptors inhibitor such as NP137 might be a novel choice to improve the clinical outcomes of these patients. The herein proposed study will be a multicenter, open-label, randomized, Phase I/II trial with: A safety run in part to assess the safety of the therapeutic combinations for the first 6 patients enrolled in each of the therapeutic combinations independently of the tumor type. According to safety rules, these therapeutic combinations will be investigated or not in the Phase II part. A Phase II part will be then conducted using an adaptive Bayesian approach allowing to quickly stop treatment cohorts without evidence of efficacy and/or select promising treatment cohorts. The Phase II part will be initiated with a preliminary step to assess the clinical activity of the proposed therapeutic combinations in 2 tumor types before proceeding to the activation of extension phase II part of the study. For each cohorts, clinical activity will be assessed through by sequential statistical analysis at specific timepoints.

Conditions

• Endometrial Carcinoma
• Cervix Carcinoma

Interventions

Type	Name	Description
DRUG	NP137	Recombinant humanized IgG1 monoclonal antibody against Netrin 1. NP137 will be administred IV, Q3W until disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, pregnancy or SMPC guidance, whichever occurs first.
DRUG	Pembrolizumab	Humanised monoclonal anti-programmed cell death-1 (PD-1) antibody will be administred in IV Q3W. A maximum 35 cycles of treatments (approximately 2 years) with pembrolizumab can be administered to patients.
DRUG	Paclitaxel	Standard Chemotherapy agent will be administred IV, Q3W, up to 6 cycles of treatment.
DRUG	Carboplatin	Standard Chemotherapy agent will be administred IV, Q3W, up to 6 cycles of treatment.

Timeline

• Start date: 2020-12-14
• Primary completion: 2025-10-30
• Completion: 2026-07-30
• First posted: 2020-12-03
• Last updated: 2024-10-08

Locations

15 sites across 1 country: France