A Study of a Personalized Neoantigen Cancer Vaccine

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.

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.

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.