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.
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.