Vorbipiprant (CR6086) / Balstilimab (AGEN2034) Combination in Stage IV Refractory pMMR - MSS CRC, and Other Metastatic GI Cancers
- Conditions
- Metastatic Microsatellite-stable Colorectal CancerGastric CancerSolid TumorRefractory Metastatic Colorectal CancerMismatch Repair Protein ProficientMetastatic GI Cancers
- Interventions
- Registration Number
- NCT05205330
- Lead Sponsor
- Rottapharm Biotech
- Brief Summary
This Phase Ib/IIa study comprises a Main Study and a Study Extension.
The Main Study has been designed according to a 3+3 Dose Escalation/dose Expansion design in refractory pMMR-MSS mCRC patients. The fixed-dose Expansion phase will be conducted at the recommended dose for expansion (RDE), with the purpose of generating additional and more robust safety and efficacy data. 27 patients are predicted in the Dose Escalation phase and 52 in the Expansion phase, respectively.
The Study Extension explores in other metastatic GI cancers the Vorbipiprant (CR6086) RDE obtained in the Main Study. 27 patients are predicted.
No control arm was included, as the target patient population of this study consists of patients in whom the overall survival is less than 6 months and treatment options are very limited and often poorly tolerated, making unlikely that the study results can be significantly biased.
- Detailed Description
In this study, the combination of the PGE2 inhibition (through the EP4 receptor antagonist CR6086) with the immune checkpoint blockade (through the anti-PD-1 AGEN2034) is being evaluated in refractory pMMR-MSS mCRC and other metastatic GI cancers. CR6086 (Vorbipiprant) is a potent and selective, orally bioavailable, targeted immunomodulator small molecule acting as an EP4 receptor antagonist. AGEN2034 (balstilimab) is a novel, fully human monoclonal immunoglobulin G4 antibody, designed to block programmed cell death 1 (PD-1) from interacting with its ligands (PD-L) PD-L1 and PD-L2, currently being developed for the treatment of advanced malignancies. EP4 receptor antagonists turn the status of the tumor microenvironment into a favourable one, i.e. immune-responsive, representing thus a rational therapeutic approach in combination with ICIs in primarily refractory cancers.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 107
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description other mGI cancers AGEN2034 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days Expansion in MSS/pMMR mCRC patients CR6086 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days Expansion in MSS/pMMR mCRC patients AGEN2034 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days 30 mg (Dose Level 1) CR6086 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 30 mg twice a day for 14 days 30 mg (Dose Level 1) AGEN2034 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 30 mg twice a day for 14 days 90 mg (Dose Level 2) CR6086 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days 90 mg (Dose Level 2) AGEN2034 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days 180 mg (Dose Level 3) CR6086 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 180 mg twice a day for 14 days 180 mg (Dose Level 3) AGEN2034 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 180 mg twice a day for 14 days other mGI cancers CR6086 14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
- Primary Outcome Measures
Name Time Method Safety and Tolerability of CR6086 combined with AGEN2034 From the time of the first dose up to 24 weeks of treatment Incidence of TEAEs using NCI CTCAE v5.0
Objective Response Rate (ORR) up to 24 weeks of treatment Proportion of patients who have achieved CR or PR per RECIST 1.1 / iRECIST during the Expansion part (Phase IIa)
Disease Control rate (DCR) up to 24 weeks of treatment Proportion of patients who have achieved CR, PR, or stable disease (SD) per RECIST 1.1 / iRECIST during the Dose Escalation part
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) throughout the study Proportion of patients who have achieved CR, PR, or stable disease (SD) per RECIST 1.1 / iRECIST during the Dose Escalation part
Objective Response Rate (ORR) throughout the study Proportion of patients who have achieved CR or PR per RECIST 1.1 / iRECIST during the Expansion part (Phase IIa)
Duration Of Response (DOR) throughout the study, up to 2 years Time from first documentation of response (CR or PR) until the time of first documentation of disease progression per RECIST 1.1 / iRECIST
Progression-Free Survival (PFR) throughout the study, up to 2 years Time from the first dose of study drugs to the earlier date of assessment of progression per RECIST 1.1 / iRECIST, or death by any cause in the absence of progression
Progression-Free Survival Rate (PFSR) throughout the study, up to 2 years Proportion of patients alive and free of disease progression per RECIST 1.1 / iRECIST at specific timepoints, or death by any cause in the absence of progression
Overall Survival (OS) throughout the study, up to 2 years Time from the first dose of study drugs to the date of death by any cause
Safety and Tolerability of CR6086 combined with AGEN2034 throughout the study, up to 2 years Incidence of TEAEs
Trial Locations
- Locations (3)
Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Istituto Oncologico Veneto IRCCS🇮🇹Padova, Italy