NCT05205330

Vorbipiprant (CR6086) / Balstilimab (AGEN2034) Combination in Stage IV Refractory pMMR - MSS CRC, and Other Metastatic GI Cancers

An Open-label, Single-arm, Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of the EP4 Receptor Antagonist Vorbipiprant (CR6086) in Combination With the PD-1 Inhibitor Balstilimab (AGEN2034), in Patients With Pretreated Mismatch-repair-proficient and Microsatellite Stable Metastatic Colorectal Cancer, and Other Metastatic GI Cancers.

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 107 (estimated)
• Sponsor: Rottapharm Biotech · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Refractory Metastatic Colorectal Cancer
• Solid Tumor
• Metastatic Microsatellite-stable Colorectal Cancer
• Mismatch Repair Protein Proficient
• Metastatic GI Cancers
• Gastric Cancer

Interventions

Type	Name	Description
DRUG	CR6086	oral CR6086, twice a day for 14 days
BIOLOGICAL	AGEN2034	AGEN2034 3 mg/Kg iv on D1 of each 14- day cycle

Timeline

• Start date: 2021-11-23
• Primary completion: 2026-12-01
• Completion: 2027-06-01
• First posted: 2022-01-25
• Last updated: 2025-10-29

Locations

3 sites across 1 country: Italy

Regulatory

• FDA-regulated drug study