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

NCT05205330 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: CR6086-1-042024-515446-16-002020-002435-29
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

prostaglandin E2 (PGE2); EP4 antagonist; CR6086; Balstilimab; anti PD-1; immune checkpoint inhibitors; Immuno-Oncology; vorbipiprant

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability of CR6086 combined with AGEN2034

  Incidence of TEAEs using NCI CTCAE v5.0

  From the time of the first dose up to 24 weeks of treatment

• Disease Control rate (DCR)

  Proportion of patients who have achieved CR, PR, or stable disease (SD) per RECIST 1.1 / iRECIST during the Dose Escalation part

  up to 24 weeks of treatment

• Objective Response Rate (ORR)

  Proportion of patients who have achieved CR or PR per RECIST 1.1 / iRECIST during the Expansion part (Phase IIa)

  up to 24 weeks of treatment

Secondary Outcomes (7)

• Disease Control Rate (DCR)

  throughout the study

• Objective Response Rate (ORR)

  throughout the study

• Duration Of Response (DOR)

  throughout the study, up to 2 years

• Progression-Free Survival (PFR)

  throughout the study, up to 2 years

• Progression-Free Survival Rate (PFSR)

  throughout the study, up to 2 years

Other Outcomes (1)

• Evaluate PD-L1 expression by CPS as predictor of response (Main Study/Expansion)

  throughout the study

Study Arms (5)

30 mg (Dose Level 1)

EXPERIMENTAL

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

Drug: CR6086; Biological: AGEN2034

90 mg (Dose Level 2)

EXPERIMENTAL

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

Drug: CR6086; Biological: AGEN2034

180 mg (Dose Level 3)

EXPERIMENTAL

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

Drug: CR6086; Biological: AGEN2034

other mGI cancers

EXPERIMENTAL

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

Drug: CR6086; Biological: AGEN2034

Expansion in MSS/pMMR mCRC patients

EXPERIMENTAL

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

Drug: CR6086; Biological: AGEN2034

Interventions

CR6086 DRUG

oral CR6086, twice a day for 14 days

Also known as: vorbipiprant

180 mg (Dose Level 3); 30 mg (Dose Level 1); 90 mg (Dose Level 2); Expansion in MSS/pMMR mCRC patients; other mGI cancers

AGEN2034 BIOLOGICAL

AGEN2034 3 mg/Kg iv on D1 of each 14- day cycle

Also known as: balstilimab

180 mg (Dose Level 3); 30 mg (Dose Level 1); 90 mg (Dose Level 2); Expansion in MSS/pMMR mCRC patients; other mGI cancers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Main Study - patients with MSS mCRC These criteria are applicable for both Dose Escalation and Expansion part of the Main Study; criteria specific for each study part are identified with ESC=Escalation or EXP=Expansion.
• Signed and dated informed consent obtained before undergoing any study-specific procedure
• Male or female aged ≥18 years
• ESC - Histologically confirmed diagnosis of adenocarcinoma originating from the colon or rectum, with known RAS and BRAF mutational status as assessed per standard practice.
• EXP - Histologically confirmed diagnosis of adenocarcinoma originating from the colon or rectum, with known RAS and BRAF mutational status as assessed per standard practice.
• For patients included in the Expansion part only: PD-L1 CPS or adequate tissue to perform PD-L1 CPS assessment should be available.
• Stage IV (according to the American Joint Committee on Cancer definition)
• Presence of measurable disease per RECIST v1.1 (based on imaging within 28 days from first study drug administration). Patients must have at least one "target lesion" to be used to assess response, as defined by RECIST v1.1 Note: Subjects with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately
• ESC - Disease progression after at least two standard treatment lines for mCRC, including fluoropyrimidines, oxaliplatin and irinotecan and, if RAS and BRAF wild-type, cetuximab or panitumumab or, intolerance or refusal of chemotherapy regimens for mCRC Note: Previous oxaliplatin-based adjuvant treatment is considered as a treatment line if disease relapse occurred within 6 months from its completion
• EXP - Disease progression after at least two standard treatment lines for mCRC, including fluoropyrimidines, oxaliplatin and irinotecan and:
• if RAS and BRAF wild type, cetuximab or panitumumab
• if BRAFV600E mutated encorafenib and cetuximab or intolerance or refusal of chemotherapy regimens for mCRC. Note: Previous oxaliplatin-based adjuvant treatment is considered as a treatment line if disease relapse occurred within 6 months from its completion 7. Naïve to any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints inhibitors) and EP4 receptor antagonists 8. ESC - Availability of adequate and sufficient baseline tumour tissue sample (archival or newly obtained biopsy) Note: an adequate and sufficient sample is defined as formalin fixed paraffin embedded tumour tissue sample, preferably from the most recent biopsy of a tumour lesion, collected either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated. If no tumour tissue is available, a fresh tissue from needle or excisional biopsy or from resection is required EXP - Availability of adequate and sufficient newly obtained fresh tumour tissue sample collected after ICF during the screening period and before the treatment starts. In case the biopsy collection is not feasible, according to Investigator judgement or patient decision, archival biopsy or surgical sample can be accepted after discussion with the Sponsor.
• Note: an adequate and sufficient sample is defined as formalin fixed paraffin embedded tumour tissue sample, collected from a site not previously irradiated. If the formalin fixed paraffin embedded tumor tissue sample obtained after the last treatment line and 90 days before the ICF signature, the patient is considered eligible, If the fresh tissue from needle or excisional biopsy/resection is not feasible according to the Investigator judgement, the patients may be eligible after discussion with the Sponsor.
• \. pMMR/MSS defined as CRC with all 4 MMR proteins intact and/or with instability at ≤1/5 locus (or 30% of loci if larger panel of markers are assayed) 10. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 11. Anticipated life expectancy ≥ 3 months 12. Adequate hematologic and end organ function, defined by the following laboratory results, obtained within 7 days before first dose of study drug treatment:
• Hemoglobin ≥ 10 g/dL, platelet count ≥100,000/mm3, ANC ≥1500/mm3

Sponsors & Collaborators

• Rottapharm Biotech: lead
• Agenus Inc.: collaborator

Study Sites (3)

Istituto Nazionale dei Tumori

Milan, Milano, 20133, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, Padova, 35128, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Pisa, 56126, Italy

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms

Interventions

balstilimab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Study Officials

• Coordinating Investigator

  IRCCS Istituto Nazionale dei Tumori

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, open label, non-randomized, single-arm (non-controlled), multiple ascending dose (Dose Escalation) in refractory pMMR-MSS mCRC patients, followed by a fixed-dose Expansion (at RDE) in refractory pMMR-MSS mCRC patients, and a fixed-dose (at RDE) Study Extension in other metastatic GI cancers

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: January 25, 2022
• Study Start: November 23, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)