A Study of a Personalized Neoantigen Cancer Vaccine

NCT ID: NCT03639714

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-13
• Study Completion Date: 2022-11-10

Brief 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.

Detailed 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.

Conditions

Non Small Cell Lung Cancer; Colorectal Cancer; Gastroesophageal Adenocarcinoma; Urothelial Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1

• GRT-C901
• GRT-R902
• nivolumab
• ipilimumab

Group Type: EXPERIMENTAL

GRT-C901

Intervention Type: BIOLOGICAL

a patient-specific neoantigen cancer vaccine prime

GRT-R902

Intervention Type: BIOLOGICAL

a patient-specific neoantigen cancer vaccine boost

nivolumab

Intervention Type: BIOLOGICAL

anti-PD-1 monoclonal antibody

ipilimumab

Intervention Type: BIOLOGICAL

anti-CTLA-4 monoclonal antibody

Phase 2 Cohorts

• GRT-C901
• GRT-R902
• nivolumab
• ipilimumab

Group Type: EXPERIMENTAL

GRT-C901

Intervention Type: BIOLOGICAL

a patient-specific neoantigen cancer vaccine prime

GRT-R902

Intervention Type: BIOLOGICAL

a patient-specific neoantigen cancer vaccine boost

nivolumab

Intervention Type: BIOLOGICAL

anti-PD-1 monoclonal antibody

ipilimumab

Intervention Type: BIOLOGICAL

anti-CTLA-4 monoclonal antibody

Interventions

GRT-C901

a patient-specific neoantigen cancer vaccine prime

Intervention Type: BIOLOGICAL

GRT-R902

a patient-specific neoantigen cancer vaccine boost

Intervention Type: BIOLOGICAL

nivolumab

anti-PD-1 monoclonal antibody

Intervention Type: BIOLOGICAL

ipilimumab

anti-CTLA-4 monoclonal antibody

Intervention Type: BIOLOGICAL

Other Intervention Names

Opdivo; Yervoy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Gritstone bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

The University of Chicago

Chicago, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Countries

United States; Australia

References

Palmer CD, Rappaport AR, Davis MJ, Hart MG, Scallan CD, Hong SJ, Gitlin L, Kraemer LD, Kounlavouth S, Yang A, Smith L, Schenk D, Skoberne M, Taquechel K, Marrali M, Jaroslavsky JR, Nganje CN, Maloney E, Zhou R, Navarro-Gomez D, Greene AC, Grotenbreg G, Greer R, Blair W, Cao MD, Chan S, Bae K, Spira AI, Roychowdhury S, Carbone DP, Henick BS, Drake CG, Solomon BJ, Ahn DH, Mahipal A, Maron SB, Johnson B, Rousseau R, Yelensky R, Liao CY, Catenacci DVT, Allen A, Ferguson AR, Jooss K. Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results. Nat Med. 2022 Aug;28(8):1619-1629. doi: 10.1038/s41591-022-01937-6. Epub 2022 Aug 15.

Reference Type: DERIVED

PMID: 35970920 (View on PubMed)

Other Identifiers

GO-004

Identifier Type: -

Identifier Source: org_study_id