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

A Phase 2/3, Randomized, Open-Label Study of Maintenance GRT-C901/GRT-R902, A Neoantigen Vaccine, in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: GRT-C901; Drug: GRT-R902; Drug: Atezolizumab; Drug: Ipilimumab; Drug: Fluoropyrimidine plus leucovorin; Drug: Bevacizumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology
  • California
    • Los Angeles, California, United States, 90033
      • U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology
    • Orange, California, United States, 92697
      • University of California - Irvine (UCI)
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles (UCLA)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers - USOR
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern CT Hematology and Oncology Associates (ECHO)
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute - Boca Raton Regional Hospital
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health South Florida (USOR site)
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • Orlando Health
    • Tamarac, Florida, United States, 33321
      • Advanced Research (Oncology & Hemotology Associates of West Broward)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60607
      • University of Illinois at Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland, PA
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
    • Florham Park, New Jersey, United States, 07932
      • Summit Health
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • Port Jefferson Station, New York, United States, 11776
      • New York Cancer and Blood
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Christ Hospital Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Northwest Cancer Specialists DBA Compass Oncology - USOR
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Medical College at Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology PA - USOR
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Dallas Sammons
    • Houston, Texas, United States, 77030
      • MD Anderson
    • Temple, Texas, United States, 76508
      • Baylor Scott and White
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Phase 2: Molecular response defined as ≥ 30% decrease from baseline in circulating tumor DNA (ctDNA)		Baseline and up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 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: 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)
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	VPS = Vaccine Production Stage; STS = Study Treatment Stage	Phase 2 up to 27 months, Phase 3 up to 60 months

Collaborators and Investigators

• Sponsor: Gritstone bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: November 19, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; colon; CRC; rectum; rectal; mCRC; personalized cancer vaccine; MSS-CRC; Colorectal cancer vaccine; personal cancer vaccine; individualized cancer vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Immune Checkpoint Inhibitors; Antidotes; Vitamin B Complex; Bevacizumab; Leucovorin; Ipilimumab; Atezolizumab
• Other Study ID Numbers: GO-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No