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

Colorectal Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05141721
• Other study ID #: GO-010
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: February 12, 2022
• Est. completion date: March 2027

Study information

• Verified date: April 2023
• Source: Gritstone bio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 700
• Est. completion date: March 2027
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

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.
• 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.
• Atezolizumab
Atezolizumab will be administered via intravenous (IV) infusion at a dose of 1680 mg once every 4 weeks.
• 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.
• Fluoropyrimidine plus leucovorin
Fluoropyrimidine (infusional 5-FU or capecitabine) and leucovorin administered as maintenance therapy per standard of care.
• Bevacizumab
Bevacizumab administered as maintenance therapy per standard of care.

Locations

Country	Name	City	State
United States	Texas Oncology PA - USOR	Austin	Texas
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	Lynn Cancer Institute - Boca Raton Regional Hospital	Boca Raton	Florida
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Christ Hospital Cancer Center	Cincinnati	Ohio
United States	Texas Oncology - Dallas Sammons	Dallas	Texas
United States	Rocky Mountain Cancer Centers - USOR	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	University of Kansas Medical Center	Fairway	Kansas
United States	Summit Health	Florham Park	New Jersey
United States	Banner MD Anderson	Gilbert	Arizona
United States	Prisma Health	Greenville	South Carolina
United States	MD Anderson	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Miami Cancer Institute at Baptist Health South Florida (USOR site)	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Tennessee Oncology - Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers	New Brunswick	New Jersey
United States	Columbia University Irving Medical Center	New York	New York
United States	NYU Langone Health	New York	New York
United States	Eastern CT Hematology and Oncology Associates (ECHO)	Norwich	Connecticut
United States	University of California - Irvine (UCI)	Orange	California
United States	Orlando Health	Orlando	Florida
United States	Sidney Kimmel Medical College at Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	New York Cancer and Blood	Port Jefferson Station	New York
United States	Northwest Cancer Specialists DBA Compass Oncology - USOR	Portland	Oregon
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	University of California Los Angeles (UCLA)	Santa Monica	California
United States	Highlands Oncology	Springdale	Arkansas
United States	Advanced Research (Oncology & Hemotology Associates of West Broward)	Tamarac	Florida
United States	Baylor Scott and White	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gritstone bio, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 2: Molecular response defined as = 30% decrease from baseline in circulating tumor DNA (ctDNA)		Baseline and up to 27 months
Primary	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	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
Secondary	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
Secondary	Phase 3: Progression-free survival per RECIST v1.1 as assessed by blinded IRC		Up to 60 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)