Clinical trial NCT03639714: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Gritstone bio, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-08-21
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
timeFrame: Initiation of study treatment through 100 days post-last dose (up to approximately 27 months)
measure: Objective Response Rate (ORR) in Phase 2 using RECIST v1.1
timeFrame: Initiation of study treatment until disease progression (up to approximately 27 months)
measure: Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902
timeFrame: Up to approximately 6 months
Secondary outcomes:
measure: Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902
timeFrame: Baseline to end of treatment (up to approximately 12 months)
measure: Objective Response Rate (ORR) in Phase 1 using RECIST v1.1
timeFrame: Initiation of study treatment until disease progression (up to approximately 4 years)
measure: Duration of response (DOR) using RECIST v1.1
timeFrame: Initiation of study treatment until disease progression (up to approximately 4 years)
measure: Clinical benefit rate (using RECIST v1.1)
timeFrame: Initiation of study treatment until disease progression (up to approximately 4 years)
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 4 years
measure: Overall survival (OS)
timeFrame: Up to approximately 4 years
measure: Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing
timeFrame: Study enrollment to initiation of study treatment (up to approximately 6 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
References:
citation: 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.