NCT03871959

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

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Pembrolizumab	200 mg, intravenous (IV), to be administered on Day 1 of every 3-week cycle i.e. Q3W.
DRUG	DEBIO1143	3 escalating dose level (100 mg, 150 mg, 200 mg) of Debio 1143 administered daily for 14 days over a 21-day cycle period.

Timeline

• Start date: 2019-09-15
• Primary completion: 2022-05-30
• Completion: 2022-06-08
• First posted: 2019-03-12
• Last updated: 2023-02-17

Locations

1 site across 1 country: France