NCT05141721

A Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer

A Phase 2/3, Randomized, Open-Label Study of Maintenance GRT-C901/GRT-R902, A Neoantigen Vaccine, in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer

• Status: Active Not Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 700 (estimated)
• Sponsor: Seattle Project Corporation · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of the Phase 2 portion of the study is to characterize the clinical activity of maintenance therapy with GRT-C901/GRT-R902 (patient-specific vaccines) in combination with checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus a fluoropyrimidine/bevacizumab alone as assessed by molecular response which is based on changes in circulating tumor (ct)DNA. The primary objective of the Phase 3 portion is to demonstrate clinical efficacy of the regimen as assessed by progression-free survival.

Detailed description

Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of human leukocyte antigens (HLAs) on the tumor cell surface. A fraction of mutated peptides result in neoantigens capable of generating T-cell responses that exclusively target tumor cells. Sensitive detection of these mutations allows for the identification of neoantigens unique to each patient's tumor to be included in a patient-specific cancer vaccine that targets these neoantigens. This vaccine regimen uses two vaccine vectors as a heterologous prime/boost approach (GRT-C901 first followed by GRT-R902) to stimulate an immune response. This study will explore the anti-tumor activity of this patient-specific immunotherapy in combination with checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab.

Conditions

• Colorectal Neoplasms

Interventions

Type	Name	Description
DRUG	GRT-C901	A patient-specific neoantigen cancer vaccine administered via intramuscular (IM) injection as prime and single boost at a dose of 1x10\^12 viral particles 2 times over the course of the first year.
DRUG	GRT-R902	A patient-specific neoantigen cancer vaccine boost, administered via IM injection at a dose of 30ug 4 times over the course of the first year.
DRUG	Atezolizumab	Atezolizumab will be administered via intravenous (IV) infusion at a dose of 1680 mg once every 4 weeks.
DRUG	Ipilimumab	Ipilimumab will be administered via subcutaneous (SC) injection at a dose of 30 mg with the first dose of GRT-C901 and GRT-R902.
DRUG	Fluoropyrimidine plus leucovorin	Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care.
DRUG	Bevacizumab	Bevacizumab administered as maintenance therapy per standard of care.

Timeline

• Start date: 2022-02-12
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2021-12-02
• Last updated: 2025-05-16

Locations

43 sites across 1 country: United States

Regulatory

• FDA-regulated drug study