A Study of a Patient-Specific Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer

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Gritstone Bio

Status and phase

Active, not recruiting
Phase 3
Phase 2

Conditions

Colorectal Neoplasms

Treatments

Drug: Ipilimumab
Drug: Atezolizumab
Drug: Fluoropyrimidine plus leucovorin
Drug: GRT-C901
Drug: GRT-R902
Drug: Bevacizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT05141721
GO-010

Details and patient eligibility

About

The primary objective of the Phase 2 portion of the study is to characterize the clinical activity of maintenance therapy with GRT-C901/GRT-R902 (patient-specific vaccines) in combination with checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus a fluoropyrimidine/bevacizumab alone as assessed by molecular response which is based on changes in circulating tumor (ct)DNA. The primary objective of the Phase 3 portion is to demonstrate clinical efficacy of the regimen as assessed by progression-free survival.

Full description

Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of human leukocyte antigens (HLAs) 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 patient-specific 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 anti-tumor activity of this patient-specific immunotherapy in combination with checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab.

Enrollment

700 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

* Patients with histologically confirmed metastatic colorectal cancer (CRC) who are planned for, or have received \<30 days of first-line treatment in the metastatic setting with FOLFOX/bev, CAPEOX/bev, FOLFOXIRI/bev, or CAPOXIRI/bev per SOC * Measurable and unresectable metastatic disease according to RECIST v1.1 * Availability of formalin-fixed paraffin-embedded (FFPE) tumor specimens. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Patient has adequate organ function per defined criteria * If women of childbearing potential (WCBP), must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 150 days after last investigational study treatment.

Exclusion criteria

* Patients with deficient mismatch repair (dMMR) or microsatellite instability (MSI-H) phenotype * Patient has a known tumor mutation burden \<1 non-synonymous mutations/megabase * Known DNA Polymerase Epsilon mutations * Patients with known BRAFV600E mutations * Bleeding disorder or history of significant bruising or bleeding following IM injections or blood draws * Immunosuppression anticipated at time of study treatment * History of allogeneic tissue/solid organ transplant * Active or history of autoimmune disease or immune deficiency * Patient with symptomatic or actively progressing central nervous system (CNS) metastases, carcinomatous meningitis, or has been treated with whole brain radiation * History of other cancer within 2 years with the exception of neoplasm that has undergone potentially curative therapy * Any severe concurrent non-cancer disease that, in the judgment of the Investigator, would make the patient inappropriate for the current study * Active tuberculosis or recent (\<2 weeks) clinically significant infection, evidence of active hepatitis B or hepatitis C, or known history of positive test for HIV * History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis) * Myocardial infarction within previous 3 months, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure (Class III or IV). * Pregnant, planning to become pregnant, or nursing.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

700 participants in 2 patient groups

Vaccine Arm
Experimental group
Description:
After receiving up to 24 weeks induction therapy with a fluoropyrimidine/oxaliplatin/bevacizumab (with or without irinotecan), per standard of care and after completing vaccine production screening, patients will receive a total of 6 administrations of GRT-C901/GRT-R902 plus ipilimumab co-administered only with the first dose of GRT-C901 and GRT-R902. All patients will receive atezolizumab in addition to maintenance therapy of a fluoropyrimidine and bevacizumab according to standard of care.
Treatment:
Drug: Bevacizumab
Drug: GRT-R902
Drug: Fluoropyrimidine plus leucovorin
Drug: GRT-C901
Drug: Atezolizumab
Drug: Ipilimumab
Control Arm
Active Comparator group
Description:
After receiving up to 24 weeks induction therapy with a fluoropyrimidine/oxaliplatin/bevacizumab (with or without irinotecan), per standard of care and undergoing vaccine production screening, patients will receive maintenance therapy of a fluoropyrimidine and bevacizumab according to standard of care.
Treatment:
Drug: Bevacizumab
Drug: Fluoropyrimidine plus leucovorin

Trial contacts and locations

43

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Central trial contact

Brian Chauder; Natasha Goodson

Data sourced from clinicaltrials.gov

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