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

NCT ID: NCT05141721

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 700 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-12
• Study Completion Date: 2027-03-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GRT-C901

Intervention Type: DRUG

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.

GRT-R902

Intervention Type: DRUG

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered via intravenous (IV) infusion at a dose of 1680 mg once every 4 weeks.

Ipilimumab

Intervention Type: DRUG

Ipilimumab will be administered via subcutaneous (SC) injection at a dose of 30 mg with the first dose of GRT-C901 and GRT-R902.

Fluoropyrimidine plus leucovorin

Intervention Type: DRUG

Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care.

Bevacizumab

Intervention Type: DRUG

Bevacizumab administered as maintenance therapy per standard of care.

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.

Group Type: ACTIVE_COMPARATOR

Fluoropyrimidine plus leucovorin

Intervention Type: DRUG

Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care.

Bevacizumab

Intervention Type: DRUG

Bevacizumab administered as maintenance therapy per standard of care.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be administered via intravenous (IV) infusion at a dose of 1680 mg once every 4 weeks.

Intervention Type: 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.

Intervention Type: DRUG

Fluoropyrimidine plus leucovorin

Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care.

Intervention Type: DRUG

Bevacizumab

Bevacizumab administered as maintenance therapy per standard of care.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Yervoy; Xeloda; Avastin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seattle Project Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Banner MD Anderson

Gilbert, Arizona, United States

Highlands Oncology

Springdale, Arkansas, United States

U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology

Los Angeles, California, United States

University of California - Irvine (UCI)

Orange, California, United States

University of California Los Angeles (UCLA)

Santa Monica, California, United States

Rocky Mountain Cancer Centers - USOR

Denver, Colorado, United States

Eastern CT Hematology and Oncology Associates (ECHO)

Norwich, Connecticut, United States

Lynn Cancer Institute - Boca Raton Regional Hospital

Boca Raton, Florida, United States

University of Miami

Miami, Florida, United States

Miami Cancer Institute at Baptist Health South Florida (USOR site)

Miami, Florida, United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Orlando Health

Orlando, Florida, United States

Advanced Research (Oncology & Hemotology Associates of West Broward)

Tamarac, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas Medical Center

Fairway, Kansas, United States

Norton Cancer Institute

Louisville, Kentucky, United States

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Astera Cancer Care

East Brunswick, New Jersey, United States

Summit Health

Florham Park, New Jersey, United States

Morristown Medical Center

Morristown, New Jersey, United States

Rutgers

New Brunswick, New Jersey, United States

NYU Langone Health

New York, New York, United States

Columbia University Irving Medical Center

New York, New York, United States

New York Cancer and Blood

Port Jefferson Station, New York, United States

Christ Hospital Cancer Center

Cincinnati, Ohio, United States

Northwest Cancer Specialists DBA Compass Oncology - USOR

Portland, Oregon, United States

Sidney Kimmel Medical College at Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Prisma Health

Greenville, South Carolina, United States

Tennessee Oncology - Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Oncology PA - USOR

Austin, Texas, United States

Texas Oncology - Dallas Sammons

Dallas, Texas, United States

MD Anderson

Houston, Texas, United States

Baylor Scott and White

Temple, Texas, United States

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

GO-010

Identifier Type: -

Identifier Source: org_study_id