Vanderbilt Clinical Trials

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

Purpose

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.

Condition

Colorectal Neoplasms

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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.

Study Design

Phase: Phase 2/Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Vaccine Arm	After receiving up to 24 weeks induction therapy with a fluoropyrimidine/oxaliplatin/bevacizumab (with or without irinotecan), per standard of care and after completing vaccine production screening, patients will receive a total of 6 administrations of GRT-C901/GRT-R902 plus ipilimumab co-administered only with the first dose of GRT-C901 and GRT-R902. All patients will receive atezolizumab in addition to maintenance therapy of a fluoropyrimidine and bevacizumab according to standard of care.	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. Other names: Tecentriq 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. Other names: Yervoy Drug: Fluoropyrimidine plus leucovorin Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care. Other names: Xeloda Drug: Bevacizumab Bevacizumab administered as maintenance therapy per standard of care. Other names: Avastin
Active Comparator Control Arm	After receiving up to 24 weeks induction therapy with a fluoropyrimidine/oxaliplatin/bevacizumab (with or without irinotecan), per standard of care and undergoing vaccine production screening, patients will receive maintenance therapy of a fluoropyrimidine and bevacizumab according to standard of care.	Drug: Fluoropyrimidine plus leucovorin Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care. Other names: Xeloda Drug: Bevacizumab Bevacizumab administered as maintenance therapy per standard of care. Other names: Avastin

More Details

Status: Active, not recruiting
Sponsor: Gritstone bio, Inc.

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.