A Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer
Sponsor: Seattle Project Corporation
ClinicalTrials ID:NCT05141721
This study evaluates a patient-specific neoantigen vaccine regimen (GRT-C901/GRT-R902) combined with checkpoint inhibitors and standard chemotherapy in metastatic colorectal cancer. Eligible patients must have confirmed metastatic CRC, measurable disease, and adequate organ function. Interventions include personalized vaccines, atezolizumab, ipilimumab, fluoropyrimidine, and bevacizumab.
Patient Parameters
| Parameter | Options |
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Program Overview
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.
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.
Eligibility Criteria
Inclusion Criteria
- Patients with histologically confirmed metastatic colorectal cancer (CRC) who are planned for, or have received <30 days of first-line treatment in the metastatic setting with FOLFOX/bev, CAPEOX/bev, FOLFOXIRI/bev, or CAPOXIRI/bev per SOC
- Measurable and unresectable metastatic disease according to RECIST v1.1
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor specimens.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patient has adequate organ function per defined criteria
- If women of childbearing potential (WCBP), must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 150 days after last investigational study treatment.
Exclusion Criteria
- Patients with deficient mismatch repair (dMMR) or microsatellite instability (MSI-H) phenotype
- Patient has a known tumor mutation burden <1 non-synonymous mutations/megabase
- Known DNA Polymerase Epsilon mutations
- Patients with known BRAFV600E mutations
- Bleeding disorder or history of significant bruising or bleeding following IM injections or blood draws
- Immunosuppression anticipated at time of study treatment
- History of allogeneic tissue/solid organ transplant
- Active or history of autoimmune disease or immune deficiency
- Patient with symptomatic or actively progressing central nervous system (CNS) metastases, carcinomatous meningitis, or has been treated with whole brain radiation
- History of other cancer within 2 years with the exception of neoplasm that has undergone potentially curative therapy
- Any severe concurrent non-cancer disease that, in the judgment of the Investigator, would make the patient inappropriate for the current study
- Active tuberculosis or recent (<2 weeks) clinically significant infection, evidence of active hepatitis B or hepatitis C, or known history of positive test for HIV
- History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis)
- Myocardial infarction within previous 3 months, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure (Class III or IV).
- Pregnant, planning to become pregnant, or nursing.
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Banner MD Anderson | 85234 | Gilbert | Arizona |
| Highlands Oncology | 72762 | Springdale | Arkansas |
| U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology | 90033 | Los Angeles | California |
| University of California - Irvine (UCI) | 92697 | Orange | California |
| University of California Los Angeles (UCLA) | 90404 | Santa Monica | California |
| Rocky Mountain Cancer Centers - USOR | 80218 | Denver | Colorado |
| Eastern CT Hematology and Oncology Associates (ECHO) | 06360 | Norwich | Connecticut |
| Lynn Cancer Institute - Boca Raton Regional Hospital | 33486 | Boca Raton | Florida |
| University of Miami | 33136 | Miami | Florida |
| Miami Cancer Institute at Baptist Health South Florida (USOR site) | 33176 | Miami | Florida |
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