A Study of a Personalized Neoantigen Cancer Vaccine

Colorectal Cancer Clinical Trial

Official title:

An International Phase 1/2 Study of GRT-C901/GRT-R902, a Neoantigen Cancer Vaccine, in Combination With Immune Checkpoint Blockade for Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03639714
• Other study ID #: GO-004
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 13, 2019
• Est. completion date: November 10, 2022

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the safety, dose, immunogenicity and early clinical activity of GRT-C901 and GRT-R902, a personalized neoantigen cancer vaccine, in combination with nivolumab and ipilimumab, in patients with metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal adenocarcinoma, and metastatic urothelial cancer.

Description:

Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of HLA 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 personalized 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 safety and early clinical activity of this patient-specific immunotherapy intended to induce T-cell responses specific for neoantigens.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: November 10, 2022
• Est. primary completion date: November 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provide a signed and dated informed consent form prior to initiation of study-specific procedures.

• Patients with the indicated advanced or metastatic solid tumor as follows:

1. NSCLC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy (note: patients who have received anti-PD-(L)1 monotherapy are eligible)

2. GEA who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy

3. mUC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy

4. CRC-MSS who are receiving first line systemic therapy or who are planned for or have received no more than 1 cycle of second line systemic therapy including a fluoropyrimidine and oxaliplatin or irinotecan

• 18 years of age or older

• ECOG Performance Status 0 or 1

• Lesion amenable to biopsy

• Measurable disease according to RECIST v1.1

• Have adequate organ function, as measured by laboratory values (criteria listed in protocol)

Exclusion Criteria:

• Tumors with genetic characteristics as follows:

1. For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK

2. For CRC and GEA, patients with known MSI-high disease based on institutional standard

3. For CRC, patients with a known BRAF V600E mutation or patients with peritoneal carcinomatosis and for GEA, patients with peritoneal carcinomatosis as their only evidence of disease

• Patients with known central nervous system (CNS) metastases and/or carcinomatous meningitis

• Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a vaccination or allergy or hypersensitivity to study drug components

• Bleeding disorder (eg., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Transitional Cell
• Colorectal Cancer
• Gastroesophageal Adenocarcinoma
• Non Small Cell Lung Cancer
• Urothelial Carcinoma

Intervention

Biological:
• GRT-C901
a patient-specific neoantigen cancer vaccine prime
• GRT-R902
a patient-specific neoantigen cancer vaccine boost
• nivolumab
anti-PD-1 monoclonal antibody
• ipilimumab
anti-CTLA-4 monoclonal antibody

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
United States	The University of Chicago	Chicago	Illinois
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Gritstone bio, Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)		Initiation of study treatment through 100 days post-last dose (up to approximately 27 months)
Primary	Objective Response Rate (ORR) in Phase 2 using RECIST v1.1		Initiation of study treatment until disease progression (up to approximately 27 months)
Primary	Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902		Up to approximately 6 months
Secondary	Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902		Baseline to end of treatment (up to approximately 12 months)
Secondary	Objective Response Rate (ORR) in Phase 1 using RECIST v1.1		Initiation of study treatment until disease progression (up to approximately 4 years)
Secondary	Duration of response (DOR) using RECIST v1.1		Initiation of study treatment until disease progression (up to approximately 4 years)
Secondary	Clinical benefit rate (using RECIST v1.1)		Initiation of study treatment until disease progression (up to approximately 4 years)
Secondary	Progression-free survival (PFS)		Up to approximately 4 years
Secondary	Overall survival (OS)		Up to approximately 4 years
Secondary	Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing		Study enrollment to initiation of study treatment (up to approximately 6 months)