Pembrolizumab In Combination With Debio 1143 In Pancreatic and Colorectal Advanced/Metastatic Adenocarcinoma (CATRIPCA)
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|ClinicalTrials.gov Identifier: NCT03871959|
Recruitment Status : Recruiting
First Posted : March 12, 2019
Last Update Posted : May 10, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Pancreas Adenocarcinoma of the Colon Adenocarcinoma of the Rectum||Drug: Pembrolizumab Drug: DEBIO1143||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The dose escalation part will follow a classical 3+3 design. 3 to 6 patients will be enrolled at each Dose Level depending of the number of Dose Limiting Toxicities observed.|
|Masking:||None (Open Label)|
|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.|
|Actual Study Start Date :||September 15, 2019|
|Estimated Primary Completion Date :||December 15, 2021|
|Estimated Study Completion Date :||December 15, 2022|
Experimental: Pembrolizumab + Debio 1143
Pembrolizumab : 200 mg, intravenous (IV), to be administered on Day 1 of every 3-week cycle i.e. Q3W.
Debio 1143 : 3 escalating dose level (100 mg, 150 mg, 200 mg) administered daily for 14 days over a 21-day cycle period.
200 mg, intravenous (IV), to be administered on Day 1 of every 3-week cycle i.e. Q3W.
Other Name: Keytruda
3 escalating dose level (100 mg, 150 mg, 200 mg) of Debio 1143 administered daily for 14 days over a 21-day cycle period.
- Maximum Tolerated Dose [ Time Frame: 21 days ]To determine the Maximum Tolerated Dose of Debio1143 when combined with a fixed dose of Pembrolizumab.
- Recommended Dose for Phase 2 [ Time Frame: 21 days ]To determine the Recommended Dose for Phase 2 (RP2D) of Debio1143 when combined with a fixed dose of Pembrolizumab.
- Extension Part Objective Response Rate [ Time Frame: 12 weeks ]The Objective Response Rate will be defined as the proportion of patients with complete response or partial response, as per RECIST V1.1.
- Duration of response [ Time Frame: Up to 2 years ]The duration of response will be measured from the time of first documented response (Complete Response or Partial Response as per RECIST V1.1) until the first documented disease progression or death due to underlying cancer, and censored at the date of the last available tumor assessment.
- Clinical Benefit Rate [ Time Frame: 12 weeks ]The Clinical Benefit Rate will be defined as the proportion of patients with Complete Response, Partial Response or stable disease according to RECIST V1.1.
- Tumor-response efficacy 1 [ Time Frame: Up to 2 years ]The tumor-response efficacy endpoints described above will be evaluated by investigator-assessed RECIST v1.1 (Eisenhauer et al. E J Cancer 2009).
- Tumor-response efficacy 2 [ Time Frame: Up to 2 years ]The tumor-response efficacy endpoints described above will be evaluated by modified criteria for immunotherapies iRECIST (Seymour et al. Lancet Oncol 2017).
- Progression-Free Survival [ Time Frame: Up to 2 years ]Progression-Free Survival (PFS) will be measured from the C1D1 until the date of event defined as the first documented progression or death from any cause. Patients with no event at the time of the analysis will be censored at the date of the last available tumor assessment.
- Overall survival [ Time Frame: Up to 2 years ]Overall survival (OS) will measured from C1D1 to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of the last contact.
- Assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE v5.0) grade [ Time Frame: Up to 2 years ]The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE v5.0) grade.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03871959
|Contact: Philippe CASSIER, MD||+ 33 (0)4 26 55 68 email@example.com|
|Centre Léon Bérard||Recruiting|
|Lyon, France, 69373|
|Contact: Philippe Cassier, MD firstname.lastname@example.org|
|Principal Investigator: Philippe CASSIER, MD|
|Sub-Investigator: Lauriane EBERST, MD|
|Sub-Investigator: Catherine TERRET, MD|
|Sub-Investigator: Amine BOUHAMAMA, MD|
|Sub-Investigator: Armelle VINCENEUX, MD|
|Sub-Investigator: Aurélie SWALDUZ, MD|
|Principal Investigator:||Philippe CASSIER, MD||Centre Leon Berard|