Clinical trial NCT05141721: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Colorectal Neoplasms
Keywords: Colorectal cancer vaccine
mCRC
colon
rectum
CRC
rectal
immunotherapy
MSS-CRC
personal cancer vaccine
personalized cancer vaccine
individualized cancer vaccine
Lead sponsor: Seattle Project Corporation
Sponsor class: INDUSTRY
First posted: 2021-12-02
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase 2: Molecular response defined as ≥ 30% decrease from baseline in circulating tumor DNA (ctDNA)
timeFrame: Baseline and up to 27 months
measure: Phase 3: Progression-free survival per Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by blinded independent review committee (IRC)
timeFrame: Up to 60 months
Secondary outcomes:
measure: 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
timeFrame: Phase 2 up to 27 months, Phase 3 up to 60 months
measure: Phase 2 and 3: Progression-free survival per RECIST v1.1 and iRECIST as assessed by the investigator
timeFrame: Phase 2: up to 27 months, Phase 3: up to 60 months
measure: Phase 3: Progression-free survival per RECIST v1.1 as assessed by blinded IRC
timeFrame: Up to 60 months
measure: Phase 2 and 3: Overall Survival as time from randomization to death from any cause
timeFrame: Phase 2 up to 27 months, Phase 3 up to 60 months
measure: Phase 2 and 3: Overall Response Rate
timeFrame: Phase 2 up to 27 months, Phase 3 up to 60 months
measure: 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
timeFrame: Phase 2 up to 27 months, Phase 3 up to 60 months
measure: 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.
timeFrame: Phase 2 up to 27 months, Phase 3 up to 60 months
measure: 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
timeFrame: Phase 2 up to 27 months, Phase 3 up to 60 months
measure: 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.
timeFrame: Study Treatment Screening visit (up to 28 days before Day 1 of study drug administration)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology
state: Arkansas
city: Los Angeles
country: United States
facility: U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology
state: California
city: Orange
country: United States
facility: University of California - Irvine (UCI)
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - USOR
state: Colorado
city: Norwich
country: United States
facility: Eastern CT Hematology and Oncology Associates (ECHO)
state: Connecticut
city: Boca Raton
country: United States
facility: Lynn Cancer Institute - Boca Raton Regional Hospital
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health South Florida (USOR site)
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tamarac
country: United States
facility: Advanced Research (Oncology & Hemotology Associates of West Broward)
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Florham Park
country: United States
facility: Summit Health
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood
state: New York
city: Cincinnati
country: United States
facility: Christ Hospital Cancer Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists DBA Compass Oncology - USOR
state: Oregon
city: Philadelphia
country: United States
facility: Sidney Kimmel Medical College at Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology - Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology PA - USOR
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Sammons
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: