A Screening Study Targeting Tumor-specific Antigens

Completed

• Conditions: Metastatic Colorectal Cancer; Stage II/III Colon Cancer
• Interventions: Procedure: blood collection for research (next generation sequencing [NGS]); Procedure: blood collection for research (HLA typing); Procedure: blood collection for research (circulating tumor DNA [ctDNA])

• Registration Number: NCT05158621
• Lead Sponsor: Gritstone bio, Inc.

Brief Summary

The purpose of this study is to identify patients who may be eligible to participate in a separate Phase 2/3 treatment study evaluating an individualized neoantigen vaccine GRANITE for first line (1L) maintenance treatment of metastatic, microsatellite-sable colorectal cancer (MSS-CRC) sponsored by Gritstone bio. This may include the manufacturing of an individualized vaccine, which involves neoantigen prediction and generating a vaccine targeting neoantigens.

Detailed Description

The screening study can enroll multiple tumor types in multiple treatment settings for the potential inclusion in a treatment study. Patient's tumors are analyzed to determine if the patient's tumor contains sufficient mutations. This screening study is currently enrolling patients with localized colon cancer or metastatic colorectal cancer for the development of an individualized neoantigen-based cancer vaccine that requires a manufacturing period for each patient.

The process of generating an individualized neoantigen cancer vaccine involves multiple steps, including collection of patient tumor and blood specimens, performing next-generation sequencing (NGS), predicting the neoantigens to be included in the individualized vaccine, and the manufacture and release of the individualized vaccine.

Study participants will not receive any investigational treatment as part of this trial. Patients screened in this study may be able to enroll in a separate investigational treatment study sponsored by Gritstone bio, provided that the patient meets the specified eligibility criteria for that treatment study.

Study Timeline

• Study First Submitted: 2021-12-02
• Study First Submitted QC: 2021-12-02
• Study Start: 2021-12-14
• Study First Posted: 2021-12-15
• Primary Completion: 2022-08-15
• Study Completion: 2022-08-15
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-17
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• signed and dated ICF prior to initiation of study-specific procedures
• histologically confirmed metastatic CRC who are planned for or who have received no more than one cycle of first-line treatment in the advanced/metastatic setting with a fluoropyrimidine and oxaliplatin in combination with bevacizumab
• measurable and unresectable disease according to RECIST v1.1
• known KRAS status
• availability of FFPE tumor specimens from biopsy within the previous 12 months for sequencing and neoantigen prediction
• ≥ 12 years of age
• ECOG performance status of 0 or 1 or equivalent for patients of 12-17 years of age
• adequate organ function (further defined in protocol)

Exclusion Criteria

• known microsatellite instability (MSI)hi disease based on institutional standard
• known tumor mutation burden <1 nonsynonymous mutations/MB
• patients with BRAF V600E mutations

LOCALIZED COLON CANCER

Inclusion Criteria:

• signed and dated ICF prior to initiation of study-specific procedures
• high-risk stage II or stage III colon cancer planned for or have completed surgical resection and have not initiated or received more than 4 weeks of adjuvant chemotherapy and be known ctDNA-positive via the Signatera assay
• availability of FFPE tumor specimens for sequencing, determination of mutations for detecting and monitoring ctDNA to identify patients with minimal residual disease, and neoantigen prediction
• ≥ 12 years of age
• ECOG performance status of 0 or 1 or equivalent for patients of 12-17 years of age
• adequate organ function (further defined in protocol)

Exclusion Criteria:

• known microsatellite instability (MSI)hi disease based on institutional standard
• known tumor mutation burden <1 nonsynonymous mutations/MB

Complete list of inclusion and exclusion criteria are listed in the clinical study protocol

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Localized Colon Cancer	blood collection for research (circulating tumor DNA [ctDNA])	Eligible patients include those with high-risk Stage II or Stage III colon cancer who have MRD based on the presence of ctDNA following surgical resection. Patients with MRD will then be assessed to determine if sufficient neoantigens are identified using Gritstone's proprietary prediction algorithm, EDGE(TM), to warrant manufacturing of an individualized vaccine.
Advanced/Metastatic Colorectal Cancer	blood collection for research (next generation sequencing [NGS])	Eligible patients include those with newly-diagnosed or recurrent advanced/metastatic CRC who are initiating fluoropyrimidine and oxaliplatin (FOLFOX or CAPEOX) in combination with bevacizumab. Patients will then be assessed to determine if sufficient neoantigens are identified using Gritstone's proprietary prediction algorithm, EDGE(TM), to warrant manufacturing of an individualized vaccine. Patients with sufficient neoantigens will have vaccine manufactured while receiving FOLFOX or CAPEOX/bevacizumab.
Localized Colon Cancer	blood collection for research (HLA typing)	Eligible patients include those with high-risk Stage II or Stage III colon cancer who have MRD based on the presence of ctDNA following surgical resection. Patients with MRD will then be assessed to determine if sufficient neoantigens are identified using Gritstone's proprietary prediction algorithm, EDGE(TM), to warrant manufacturing of an individualized vaccine.
Advanced/Metastatic Colorectal Cancer	blood collection for research (HLA typing)	Eligible patients include those with newly-diagnosed or recurrent advanced/metastatic CRC who are initiating fluoropyrimidine and oxaliplatin (FOLFOX or CAPEOX) in combination with bevacizumab. Patients will then be assessed to determine if sufficient neoantigens are identified using Gritstone's proprietary prediction algorithm, EDGE(TM), to warrant manufacturing of an individualized vaccine. Patients with sufficient neoantigens will have vaccine manufactured while receiving FOLFOX or CAPEOX/bevacizumab.
Localized Colon Cancer	blood collection for research (next generation sequencing [NGS])	Eligible patients include those with high-risk Stage II or Stage III colon cancer who have MRD based on the presence of ctDNA following surgical resection. Patients with MRD will then be assessed to determine if sufficient neoantigens are identified using Gritstone's proprietary prediction algorithm, EDGE(TM), to warrant manufacturing of an individualized vaccine.

Primary Outcome Measures

Name	Time	Method
Primary	at study enrollment	To identify patients with a defined tumor-specific profile (or tumor-specific characteristics, proteins, mutations) for potential inclusion in a separate clinical study that involves investigational study treatment.

Trial Locations

Locations (6)

Advanced Research; 🇺🇸 Tamarac, Florida, United States

Astera Cancer Care; 🇺🇸 East Brunswick, New Jersey, United States

Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Sarah Cannon; 🇺🇸 Nashville, Tennessee, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States