A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

NCT ID: NCT03953235

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-18
• Study Completion Date: 2023-03-10

Brief Summary

The purpose of this study is to evaluate the dose, safety, immunogenicity and early clinical activity of GRT-C903 and GRT-R904, a neoantigen-based therapeutic cancer vaccine, in combination with immune checkpoint blockade, in patients with advanced or metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, pancreatic cancer, and shared neoantigen-positive tumors. Based on the Phase 1 data, an updated vaccine candidate (SLATE-KRAS or version 2) was developed that removed 16 of the 20 mutations included in the original vaccine (version 1) and solely targets KRAS mutations.

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. Some of these tumor-specific neoantigens are known or expected to be common across a subset of patients and are called shared neoantigens. This study aims to target shared neoantigens using a heterologous prime/boost therapeutic vaccine approach (GRT-C903 first followed by GRT-R904) in combination with checkpoint blockade to stimulate an immune response. This study will explore the safety and early clinical activity of this neoantigen-based immunotherapy intended to induce T-cell responses specific for the shared neoantigens contained within the therapeutic vaccine. Phase 1 will test multiple doses and combinations with checkpoint blockade and Phase 2 will test for early signs of clinical activity using a vaccine regimen based on Phase 1 data.

Conditions

Non-Small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Shared Neoantigen-Positive Solid Tumors

Study Design

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

Study Groups

Phase 1

• GRT-C903
• GRT-R904
• nivolumab
• ipilimumab

Group Type: EXPERIMENTAL

GRT-C903

Intervention Type: BIOLOGICAL

a shared neoantigen cancer vaccine prime

GRT-R904

Intervention Type: BIOLOGICAL

a shared neoantigen cancer vaccine boost

nivolumab

Intervention Type: BIOLOGICAL

anti-PD-1 monoclonal antibody

ipilimumab

Intervention Type: BIOLOGICAL

anti-CTLA-4 monoclonal antibody

Phase 2

• GRT-C903
• GRT-R904
• nivolumab
• ipilimumab

Phase 2 for some patients includes a monthly or every two month treatment schedule

Group Type: EXPERIMENTAL

GRT-C903

Intervention Type: BIOLOGICAL

a shared neoantigen cancer vaccine prime

GRT-R904

Intervention Type: BIOLOGICAL

a shared neoantigen cancer vaccine boost

nivolumab

Intervention Type: BIOLOGICAL

anti-PD-1 monoclonal antibody

ipilimumab

Intervention Type: BIOLOGICAL

anti-CTLA-4 monoclonal antibody

Interventions

GRT-C903

a shared neoantigen cancer vaccine prime

Intervention Type: BIOLOGICAL

GRT-R904

a shared 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

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. Microsatellite-stable colorectal cancer (MSS-CRC) who are currently receiving systemic treatment with a fluoropyrimidine and oxaliplatin and/or irinotecan that may include a VEGF or EGFR targeting therapy as their 1L therapy for metastatic disease OR who have experienced disease progression following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan that may include a VEGF or EGFR targeting therapy and have not received additional lines of systemic therapy in the metastatic setting.

2. Non-small cell lung cancer (NSCLC) who are currently receiving systemic treatment with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy OR who have experienced disease progression following treatment with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy (or anti-PD-(L)1 alone if patient refuses platinum-based chemotherapy), and have not received additional lines of systemic therapy in the metastatic setting.

3. Pancreatic ductal adenocarcinoma (PDA) who are currently receiving systemic cytotoxic chemotherapy as their 1L therapy for metastatic disease OR who have experienced disease progression on 1L systemic cytotoxic chemotherapy and have received no more than 1 prior line of therapy in the metastatic setting.

4. Any solid tumor histology where the patient has experienced disease progression with all available therapies known to confer clinical benefit

• Patient's tumor possesses one of the mutations listed below, and is determined to express a HLA allele for antigen presentation of the identified tumor mutation:

VERSION 1.0 of the expression cassette:

BRAF_G466V // CTNNB1_S37F // CTNNB1_S45F // CTNNB1_S45P // CTNNB1_T41A // ERBB2_Y772_A775dup // KRAS_G12C or NRAS_G12C // KRAS_G12D or NRAS_G12D // KRAS_G12V // KRAS_G13D // KRAS_Q61H or NRAS_Q61H // KRAS_Q61K or NRAS_Q61K // KRAS_Q61L or NRAS_Q61L // KRAS_Q61R or NRAS_Q61R // TP53_K132E // TP53_K132N // TP53_R213L // TP53_R249M // TP53_S127Y

VERSION 2.0 of the expression cassette:

KRAS_G12C or NRAS_G12C // KRAS_G12D or NRAS_G12D // KRAS_G12V or NRAS_G12V // KRAS_Q61H or NRAS_Q61H

• ECOG Performance Status 0 or 1
• Measurable disease according to RECIST v1.1
• 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. Patients with known MSI-high disease based on institutional standard

• Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a vaccination
• Bleeding disorder (eg., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws
• History of allogenic/solid organ transplant
• Active, known, or suspected autoimmune disease
• Active tuberculosis or recent (<2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C
• Known history of positive test for human immunodeficiency (HIV) or known acquired immunodeficiency syndrome (AIDS)

• 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

UCLA Medical Center

Santa Monica, California, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

University of Chicago Medicine, Comprehensive Cancer Center

Chicago, Illinois, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Countries

United States

References

Rappaport AR, Kyi C, Lane M, Hart MG, Johnson ML, Henick BS, Liao CY, Mahipal A, Shergill A, Spira AI, Goldman JW, Scallan CD, Schenk D, Palmer CD, Davis MJ, Kounlavouth S, Kemp L, Yang A, Li YJ, Likes M, Shen A, Boucher GR, Egorova M, Veres RL, Espinosa JA, Jaroslavsky JR, Kraemer Tardif LD, Acrebuche L, Puccia C, Sousa L, Zhou R, Bae K, Hecht JR, Carbone DP, Johnson B, Allen A, Ferguson AR, Jooss K. A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results. Nat Med. 2024 Apr;30(4):1013-1022. doi: 10.1038/s41591-024-02851-9. Epub 2024 Mar 27.

Reference Type: DERIVED

PMID: 38538867 (View on PubMed)

Other Identifiers

GO-005

Identifier Type: -

Identifier Source: org_study_id