A Study of a Personalized Neoantigen Cancer Vaccine

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Non Small Cell Lung Cancer, Colorectal Cancer, Gastroesophageal Adenocarcinoma, Urothelial Carcinoma

Intervention / Treatment
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* Biological: GRT-C901
* Biological: GRT-R902
* Biological: nivolumab
* Biological: ipilimumab


Participation Criteria
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Eligibility Criteria
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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: 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 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: 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 Complete inclusion and exclusion criteria are listed in the clinical study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Overall survival (OS) |  | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoantigen cancer vaccine, personalized neoantigen cancer vaccine, GRT-C901, GRT-R902, immunotherapy, nivolumab, ipilimumab, PD-1, CTLA-4