A Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Neoplasms
- Interventions
- Registration Number
- NCT05141721
- Lead Sponsor
- Seattle Project Corporation
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 700
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm Fluoropyrimidine plus leucovorin 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. Vaccine Arm Fluoropyrimidine plus leucovorin 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. Vaccine Arm GRT-C901 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. Vaccine Arm GRT-R902 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. Vaccine Arm Atezolizumab 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. Vaccine Arm Ipilimumab 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. Vaccine Arm Bevacizumab 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. Control Arm Bevacizumab 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.
- Primary Outcome Measures
Name Time Method Phase 3: Progression-free survival per Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by blinded independent review committee (IRC) Up to 60 months defined by time from randomization until disease progression as per iRECIST or death from any cause
Phase 2: Molecular response defined as ≥ 30% decrease from baseline in circulating tumor DNA (ctDNA) Baseline and up to 27 months
- Secondary Outcome Measures
Name Time Method Phase 3: Progression-free survival per RECIST v1.1 as assessed by blinded IRC Up to 60 months 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: Duration of response (DOR) defined by time from the first objective response of PR or PR until disease progression or death 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 2 and 3: Deepening of Response the proportion of patients who have a BOR of SD or PR during the VPS and who convert from SD to PR or CR, or from PR to CR after start of the study treatment and/or SOC maintenance treatment in the STS per RECIST v1.1 Phase 2 up to 27 months, Phase 3 up to 60 months VPS = Vaccine Production Stage; STS = Study Treatment Stage
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 measured by the proportion of patients with best overall response (BOR) of partial response (PR) or complete response (CR) by REICST v1.1 or , immune-based PR (iPR) or immune-based by iRECIST
Phase 2 and 3: Clinical benefit rate (CBR) as defined by the proportion of patients with best overall response of stable disease (SD), PR or CR using RECIS v1.1 or immune-based SD (iSD), iPR, or iCR by iRECIST. Phase 2 up to 27 months, Phase 3 up to 60 months Phase 2 and 3: The feasibility of manufacturing a patient-specific vaccine defined by the proportion of patients for whom vaccine was successfully manufactured from those randomized to the vaccine arm. Study Treatment Screening visit (up to 28 days before Day 1 of study drug administration)
Trial Locations
- Locations (43)
Sidney Kimmel Medical College at Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Advanced Research (Oncology & Hemotology Associates of West Broward)
🇺🇸Tamarac, Florida, United States
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
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Lynn Cancer Institute - Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
Eastern CT Hematology and Oncology Associates (ECHO)
🇺🇸Norwich, Connecticut, United States
Summit Health
🇺🇸Florham Park, New Jersey, United States
Rutgers
🇺🇸New Brunswick, New Jersey, United States
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
NYU Langone Health
🇺🇸New York, New York, United States
New York Cancer and Blood
🇺🇸Port Jefferson Station, New York, United States
Prisma Health
🇺🇸Greenville, South Carolina, United States
Texas Oncology - Dallas Sammons
🇺🇸Dallas, Texas, United States
Texas Oncology PA - USOR
🇺🇸Austin, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Baylor Scott and White
🇺🇸Temple, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Rocky Mountain Cancer Centers - USOR
🇺🇸Denver, Colorado, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Miami
🇺🇸Miami, Florida, United States
MD Anderson
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute at University of Utah
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Miami Cancer Institute at Baptist Health South Florida (USOR site)
🇺🇸Miami, Florida, United States
Orlando Health
🇺🇸Orlando, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, 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
Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
Northwest Cancer Specialists DBA Compass Oncology - USOR
🇺🇸Portland, Oregon, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Tennessee Oncology - Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Kansas Medical Center
🇺🇸Fairway, Kansas, United States