GenVivo to Present GEN2 Phase 1 Results at 2024 SITC Annual Meeting

GenVivo, Inc. (GVO), a privately held clinical-stage biopharmaceutical company, has announced the results of its Phase 1 clinical trial for GEN2. This trial involved adult patients with hepatocellular carcinoma or tumors metastatic to the liver (NCT04313868), and the findings were presented at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, Texas.

GEN2 employs a non-replicating mRNA vector to introduce two genes with dual mechanisms of action: an enhanced prodrug-activated enzyme (HSV-eTK) and an immunostimulatory cytokine (GM-CSF). Following the administration of valganciclovir, GEN2 activates the local release of tumor-specific antigens, including neoantigens, which stimulate an immune response. The therapy is quicker than conventional methods, as it bypasses the need for tumor biopsies or genomic sequencing to identify patient-specific neoantigens before treatment.

In the Phase 1 trial, 48 patients were treated with GEN2 in combination with valganciclovir (VGCV) through intravenous (IV) administration. The trial followed a three-week cycle where GEN2 was administered on Days 1, 2, and 3, and VGCV was given on Days 8 to 12. GEN2 was generally well-tolerated across various dosages, with minimal toxicity and no dose-dependent treatment-emergent adverse events (TEAEs). The exposure to the drug was linear across a 1000-fold dose range. Notably, 21% of patients continued the treatment for more than six months, with the longest duration being 21 months. No maximum tolerated dose (MTD) was identified during the study.

In the US, another Phase 1 trial (NCT06391918) began earlier this year to determine the Recommended Phase 2 Dose (RP2D) with a different IV schedule and will eventually include additional tumor types. The trial's exploratory goals encompass validating receptor binding, analyzing pre- and post-tumor biopsies, assessing cytokines, performing immunophenotyping, and evaluating the presence or absence of neutralizing antibodies to fine-tune the dosing regimen. Following the determination of the RP2D, expansion cohorts will enroll patients with hepatocellular carcinoma (HCC), hormone receptor-positive breast cancer, and skin cancers. An additional cohort will investigate intratumoral (IT) dosing in skin cancer patients, aiming to obtain paired biopsies and perform tissue correlative studies.

GEN2’s IV administration marks a significant improvement over therapies that rely on intratumoral (IT) or intralesional (IL) delivery, which are typically limited to tumors that are easily accessible. Clinical trials involving oncolytic viruses or replication-deficient vectors have shown promising outcomes in various cancers, such as skin, bladder, prostate, pancreatic, and lung cancers, impacting both injected and non-injected tumors. However, there are practical constraints to IT or IL methods. In contrast, GEN2’s IV administration can treat advanced diseases with widespread malignancies.

GenVivo, Inc. is dedicated to developing and manufacturing innovative gene delivery and immune stimulation therapies that activate the patient’s immune system to fight cancer. Their first clinical candidate, GEN2, is currently undergoing a Phase 1 trial in the US under protocol NCT06391918. The company aims to enhance cancer patient survival and improve quality of life through rapidly deployed and easily administered treatments.