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

NCT05141721 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GO-010
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 43

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.

Conditions

Colorectal Neoplasms

Keywords

Colorectal cancer vaccine; mCRC; colon; rectum; CRC; rectal; immunotherapy; MSS-CRC; personal cancer vaccine; personalized cancer vaccine; individualized cancer vaccine

Outcome Measures

Primary Outcomes (2)

• Phase 2: Molecular response defined as ≥ 30% decrease from baseline in circulating tumor DNA (ctDNA)

  Baseline and up to 27 months

• Phase 3: Progression-free survival per Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by blinded independent review committee (IRC)

  defined by time from randomization until disease progression as per iRECIST or death from any cause

  Up to 60 months

Secondary Outcomes (9)

• Phase 2 and 3: Incidence of treatment-emergent adverse events (TEAEs), immune-related AEs, treatment-related AEs, serious AEs, AEs leading to death, AEs leading to dose delays, and AEs leading to discontinuation of study treatment

  Phase 2 up to 27 months, Phase 3 up to 60 months

• Phase 2 and 3: Progression-free survival per RECIST v1.1 and iRECIST as assessed by the investigator

  Phase 2: up to 27 months, Phase 3: up to 60 months

• Phase 3: Progression-free survival per RECIST v1.1 as assessed by blinded IRC

  Up to 60 months

• Phase 2 and 3: Overall Survival as time from randomization to death from any cause

  Phase 2 up to 27 months, Phase 3 up to 60 months

• Phase 2 and 3: Overall Response Rate

  Phase 2 up to 27 months, Phase 3 up to 60 months

Study Arms (2)

Vaccine Arm

EXPERIMENTAL

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; Drug: GRT-R902; Drug: Atezolizumab; Drug: Ipilimumab; Drug: Fluoropyrimidine plus leucovorin; Drug: Bevacizumab

Control Arm

ACTIVE COMPARATOR

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; Drug: Bevacizumab

Interventions

GRT-C901 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.

Vaccine Arm

GRT-R902 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.

Vaccine Arm

Atezolizumab DRUG

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

Also known as: Tecentriq

Vaccine Arm

Ipilimumab 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.

Also known as: Yervoy

Vaccine Arm

Fluoropyrimidine plus leucovorin DRUG

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

Also known as: Xeloda

Control Arm; Vaccine Arm

Bevacizumab DRUG

Bevacizumab administered as maintenance therapy per standard of care.

Also known as: Avastin

Control Arm; Vaccine Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Seattle Project Corporation: lead

Study Sites (43)

Banner MD Anderson

Gilbert, Arizona, 85234, United States

Location

Highlands Oncology

Springdale, Arkansas, 72762, United States

Location

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

Los Angeles, California, 90033, United States

Location

University of California - Irvine (UCI)

Orange, California, 92697, United States

Location

University of California Los Angeles (UCLA)

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Centers - USOR

Denver, Colorado, 80218, United States

Location

Eastern CT Hematology and Oncology Associates (ECHO)

Norwich, Connecticut, 06360, United States

Location

Lynn Cancer Institute - Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

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

Miami, Florida, 33176, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Advanced Research (Oncology & Hemotology Associates of West Broward)

Tamarac, Florida, 33321, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89119, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

Summit Health

Florham Park, New Jersey, 07932, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Rutgers

New Brunswick, New Jersey, 08903, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

New York Cancer and Blood

Port Jefferson Station, New York, 11776, United States

Location

Christ Hospital Cancer Center

Cincinnati, Ohio, 45229, United States

Location

Northwest Cancer Specialists DBA Compass Oncology - USOR

Portland, Oregon, 97227, United States

Location

Sidney Kimmel Medical College at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Prisma Health

Greenville, South Carolina, 29615, United States

Location

Tennessee Oncology - Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology PA - USOR

Austin, Texas, 78705, United States

Location

Texas Oncology - Dallas Sammons

Dallas, Texas, 75246, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Baylor Scott and White

Temple, Texas, 76508, United States

Location

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

atezolizumab; Ipilimumab; Leucovorin; Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 2, 2021
• Study Start: February 12, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (43)