A Study of a Personalized Neoantigen Cancer Vaccine

NCT03639714 | Completed Phase 1 FDA Drug

• 1 other identifier: GO-004
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 11

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.

Conditions

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

Keywords

neoantigen cancer vaccine; personalized neoantigen cancer vaccine; GRT-C901; GRT-R902; immunotherapy; nivolumab; ipilimumab; PD-1; CTLA-4

Outcome Measures

Primary Outcomes (3)

• 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)

• Objective Response Rate (ORR) in Phase 2 using RECIST v1.1

  Initiation of study treatment until disease progression (up to approximately 27 months)

• Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902

  Up to approximately 6 months

Secondary Outcomes (7)

• Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902

  Baseline to end of treatment (up to approximately 12 months)

• Objective Response Rate (ORR) in Phase 1 using RECIST v1.1

  Initiation of study treatment until disease progression (up to approximately 4 years)

• Duration of response (DOR) using RECIST v1.1

  Initiation of study treatment until disease progression (up to approximately 4 years)

• Clinical benefit rate (using RECIST v1.1)

  Initiation of study treatment until disease progression (up to approximately 4 years)

• Progression-free survival (PFS)

  Up to approximately 4 years

Study Arms (2)

Phase 1

EXPERIMENTAL

* GRT-C901 * GRT-R902 * nivolumab * ipilimumab

Biological: GRT-C901; Biological: GRT-R902; Biological: nivolumab; Biological: ipilimumab

Phase 2 Cohorts

EXPERIMENTAL

* GRT-C901 * GRT-R902 * nivolumab * ipilimumab

Biological: GRT-C901; Biological: GRT-R902; Biological: nivolumab; Biological: ipilimumab

Interventions

GRT-C901 BIOLOGICAL

a patient-specific neoantigen cancer vaccine prime

Phase 1; Phase 2 Cohorts

GRT-R902 BIOLOGICAL

a patient-specific neoantigen cancer vaccine boost

Phase 1; Phase 2 Cohorts

nivolumab BIOLOGICAL

anti-PD-1 monoclonal antibody

Also known as: Opdivo

Phase 1; Phase 2 Cohorts

ipilimumab BIOLOGICAL

anti-CTLA-4 monoclonal antibody

Also known as: Yervoy

Phase 1; Phase 2 Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)
• GEA who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy
• mUC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy
• 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
• 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)

You may not qualify if:

• Tumors with genetic characteristics as follows:
• For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK
• For CRC and GEA, patients with known MSI-high disease based on institutional standard
• 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

Sponsors & Collaborators

• Gritstone bio, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (11)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10017, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Related Publications (1)

• 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.

  PMID: 35970920 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Carcinoma, Transitional Cell; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 21, 2018
• Study Start: February 13, 2019
• Primary Completion: November 10, 2022
• Study Completion: November 10, 2022
• Last Updated: September 13, 2023

Record last verified: 2023-09

Locations

US (10); AU (1)