A Study of a Personalized Neoantigen Cancer Vaccine

Brief Title

A Study of a Personalized Neoantigen Cancer Vaccine

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

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.

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

Secondary Outcome

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

Condition

Non Small Cell Lung Cancer

Intervention

GRT-C901

Study Arms / Comparison Groups

 Phase 1

Description:  GRT-C901
GRT-R902
nivolumab
ipilimumab

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Biological

Estimated Enrollment

Start Date

February 13, 2019

Completion Date

November 10, 2022

Primary Completion Date

November 10, 2022

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

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

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, ,

Location Countries

Australia

Location Countries

Australia

Administrative Informations

NCT ID

NCT03639714

Organization ID

GO-004

Responsible Party

Sponsor

Study Sponsor

Gritstone bio, Inc.

Collaborators

 Bristol-Myers Squibb

Study Sponsor

, ,

Verification Date

February 2023