Back to resultsA Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer
Primary Purpose
Colorectal Neoplasms
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GRT-C901
GRT-R902
Atezolizumab
Ipilimumab
Fluoropyrimidine plus leucovorin
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms focused on measuring Colorectal cancer vaccine, mCRC, colon, rectum, CRC, rectal, immunotherapy, MSS-CRC, personal cancer vaccine, personalized cancer vaccine, individualized cancer vaccine
Eligibility Criteria
Inclusion Criteria:
- Patients with histologically confirmed metastatic colorectal cancer (CRC) who are planned for, or have received no more than 1 cycle of first-line treatment in the metastatic setting with a fluoropyrimidine and oxaliplatin in combination with bevacizumab
- Measurable and unresectable 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 in opinion of investigator
- 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 high levels of 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
- Pregnant, planning to become pregnant, or nursing.
Sites / Locations
- Banner MD Anderson
- Highlands Oncology
- U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology
- University of California - Irvine (UCI)
- Sansum Clinic - USOR
- University of California Los Angeles (UCLA)
- Rocky Mountain Cancer Centers - USOR
- Eastern CT Hematology and Oncology Associates (ECHO)
- Lynn Cancer Institute - Boca Raton Regional Hospital
- Mount Sinai Comprehensive Cancer Center
- University of Miami
- Miami Cancer Institute at Baptist Health South Florida (USOR site)
- Orlando Health
- Advanced Research (Oncology & Hemotology Associates of West Broward)
- University of Illinois at Chicago
- University of Chicago
- Indiana University
- University of Kansas Medical Center
- Norton Cancer Institute
- American Oncology Partners of Maryland, PA
- Barbara Ann Karmanos Cancer Institute
- Comprehensive Cancer Centers of Nevada
- Astera Cancer Care
- Summit Health
- Morristown Medical Center
- Rutgers
- NYU Langone Health
- Columbia University Irving Medical Center
- New York Cancer and Blood
- Christ Hospital Cancer Center
- Northwest Cancer Specialists DBA Compass Oncology - USOR
- Sidney Kimmel Medical College at Thomas Jefferson University
- Allegheny General Hospital
- Prisma Health
- Tennessee Oncology - Sarah Cannon Research Institute
- Vanderbilt University Medical Center
- Texas Oncology PA - USOR
- Texas Oncology - Dallas Sammons
- MD Anderson
- Baylor Scott and White
- Huntsman Cancer Institute at University of Utah
- University of Virginia
- Virginia Cancer Specialists
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Vaccine Arm
Control Arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Phase 2: Molecular response defined as ≥ 30% decrease from baseline in circulating tumor DNA (ctDNA)
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
Secondary Outcome Measures
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 and 3: Progression-free survival per RECIST v1.1 and iRECIST as assessed by the investigator
Phase 3: Progression-free survival per RECIST v1.1 as assessed by blinded IRC
Phase 2 and 3: Overall Survival as time from randomization to death from any cause
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 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 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 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 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05141721
Brief Title
A Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 12, 2022 (Actual)
Primary Completion Date
March 2027 (Anticipated)
Study Completion Date
March 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gritstone bio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms
Keywords
Colorectal cancer vaccine, mCRC, colon, rectum, CRC, rectal, immunotherapy, MSS-CRC, personal cancer vaccine, personalized cancer vaccine, individualized cancer vaccine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
700 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vaccine Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Control Arm
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GRT-C901
Intervention Description
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
Intervention Name(s)
GRT-R902
Intervention Description
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
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab will be administered via intravenous (IV) infusion at a dose of 1680 mg once every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Yervoy
Intervention Description
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
Intervention Name(s)
Fluoropyrimidine plus leucovorin
Other Intervention Name(s)
Xeloda
Intervention Description
Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab administered as maintenance therapy per standard of care.
Primary Outcome Measure Information:
Title
Phase 2: Molecular response defined as ≥ 30% decrease from baseline in circulating tumor DNA (ctDNA)
Time Frame
Baseline and up to 27 months
Title
Phase 3: Progression-free survival per Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by blinded independent review committee (IRC)
Description
defined by time from randomization until disease progression as per iRECIST or death from any cause
Time Frame
Up to 60 months
Secondary Outcome Measure Information:
Title
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
Time Frame
Phase 2 up to 27 months, Phase 3 up to 60 months
Title
Phase 2 and 3: Progression-free survival per RECIST v1.1 and iRECIST as assessed by the investigator
Time Frame
Phase 2: up to 27 months, Phase 3: up to 60 months
Title
Phase 3: Progression-free survival per RECIST v1.1 as assessed by blinded IRC
Time Frame
Up to 60 months
Title
Phase 2 and 3: Overall Survival as time from randomization to death from any cause
Time Frame
Phase 2 up to 27 months, Phase 3 up to 60 months
Title
Phase 2 and 3: Overall Response Rate
Description
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
Time Frame
Phase 2 up to 27 months, Phase 3 up to 60 months
Title
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
Time Frame
Phase 2 up to 27 months, Phase 3 up to 60 months
Title
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.
Time Frame
Phase 2 up to 27 months, Phase 3 up to 60 months
Title
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
Description
VPS = Vaccine Production Stage; STS = Study Treatment Stage
Time Frame
Phase 2 up to 27 months, Phase 3 up to 60 months
Title
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.
Time Frame
Study Treatment Screening visit (up to 28 days before Day 1 of study drug administration)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Banner MD Anderson
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Highlands Oncology
City
Springdale
State/Province
Arkansas
ZIP/Postal Code
72762
Country
United States
Facility Name
U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California - Irvine (UCI)
City
Orange
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
Sansum Clinic - USOR
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
University of California Los Angeles (UCLA)
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Rocky Mountain Cancer Centers - USOR
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Eastern CT Hematology and Oncology Associates (ECHO)
City
Norwich
State/Province
Connecticut
ZIP/Postal Code
06360
Country
United States
Facility Name
Lynn Cancer Institute - Boca Raton Regional Hospital
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Mount Sinai Comprehensive Cancer Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Miami Cancer Institute at Baptist Health South Florida (USOR site)
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Orlando Health
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Advanced Research (Oncology & Hemotology Associates of West Broward)
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60607
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
American Oncology Partners of Maryland, PA
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119
Country
United States
Facility Name
Astera Cancer Care
City
East Brunswick
State/Province
New Jersey
ZIP/Postal Code
08816
Country
United States
Facility Name
Summit Health
City
Florham Park
State/Province
New Jersey
ZIP/Postal Code
07932
Country
United States
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Rutgers
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
New York Cancer and Blood
City
Port Jefferson Station
State/Province
New York
ZIP/Postal Code
11776
Country
United States
Facility Name
Christ Hospital Cancer Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Northwest Cancer Specialists DBA Compass Oncology - USOR
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Sidney Kimmel Medical College at Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Prisma Health
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Tennessee Oncology - Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Oncology PA - USOR
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Texas Oncology - Dallas Sammons
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Baylor Scott and White
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Huntsman Cancer Institute at University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer
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