A Study of a Personalized Neoantigen Cancer Vaccine

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Non Small Cell Lung Cancer; Gastroesophageal Adenocarcinoma; Urothelial Carcinoma
• Intervention / Treatment: Biological: nivolumab; Biological: GRT-C901; Biological: GRT-R902; Biological: ipilimumab

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10017
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; GRT-C901; GRT-R902; nivolumab; ipilimumab	Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo; Biological: GRT-C901; a patient-specific neoantigen cancer vaccine prime; Biological: GRT-R902; a patient-specific neoantigen cancer vaccine boost; Biological: ipilimumab; anti-CTLA-4 monoclonal antibody; Other Names: Yervoy
Experimental: Phase 2 Cohorts; GRT-C901; GRT-R902; nivolumab; ipilimumab	Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo; Biological: GRT-C901; a patient-specific neoantigen cancer vaccine prime; Biological: GRT-R902; a patient-specific neoantigen cancer vaccine boost; Biological: ipilimumab; anti-CTLA-4 monoclonal antibody; Other Names: Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to approximately 4 years
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
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)

Collaborators and Investigators

• Sponsor: Gritstone bio, Inc.
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2019
• Primary Completion (Actual): November 10, 2022
• Study Completion (Actual): November 10, 2022

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 18, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; PD-1; nivolumab; ipilimumab; CTLA-4; neoantigen cancer vaccine; personalized neoantigen cancer vaccine; GRT-C901; GRT-R902
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: GO-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No