Pembrolizumab In Combination With Debio 1143 In Pancreatic and Colorectal Advanced/Metastatic Adenocarcinoma — CATRIPCA  

Adenocarcinoma of the Pancreas Clinical Trial

Official title: CATRIPCA - A Phase I Study of PD1 Monoclonal Antibody (Pembrolizumab) In Combination With a IAP Antagonist (Debio 1143) In (Exocrine) Pancreatic And Colorectal Non MSI-high Advanced/Metastatic Adenocarcinoma.

Status Completed

Clinical Trial Summary

This trial is a Phase I study to be conducted in patients with non-MSI-high advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer (CRC) and is divided in two Parts.

• Dose escalation Part :To determine the Maximum Tolerated Dose (MTD) and the Recommended Dose for Phase 2 (RP2D) of Debio1143 when combined with a fixed dose of Pembrolizumab.

• Extension Part: To evaluate preliminary efficacy data of the proposed combination.

Clinical Trial Description

All patient wil receive a combinaison of Pembrolizumab and Debio 1143. Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Debio 1143 is an investigational, oral monovalent second mitochondrial-derived activator of caspases (SMAC) mimetic designed to promote programmed cell death (apoptosis) in tumor cells and anti-tumour immunity. By antagonizing the activity of inhibitor of apoptosis proteins (IAPs (X-linked IAP [XIAP], cellular IAP 1 [cIAP1], cellular IAP 2 [cIAP2] and melanoma-linked IAP [ML-IAP])), Smac mimetics are an interesting treatment approach for cancer that may foster better tumor responses to chemo/radiotherapy- and/or immuno-therapy.

A Dose escalation part (n= up to 18 patients ) aiming to define the Maximum Tolerated Dose and the the Recommended Dose for Phase 2 of the proposed combination. A classical 3+3 design will be used with a fixed dose of Pembrolizumab (200 mg, intravenous , to be administered on Day 1 of every 3-week cycle i.e. Q3W) and 3 escalating dose level of Debio 1143 administered daily for 14 days over a 21-day cycle period.

There will be a 24-hour delay between the first and subsequent patients enrolled in each DL cohort to maximize the safety of enrolled patients.

An extension part (n=28 patients: 14 patients per cohort) aiming to evaluate the clinical activity of the proposed combination. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Adenocarcinoma of the Pancreas
• Adenocarcinoma of the Rectum

• NCT number: NCT03871959
• Study type: Interventional
• Source: Centre Leon Berard
• Status: Completed
• Phase: Phase 1
• Start date: September 15, 2019
• Completion date: June 8, 2022