- GEN2 was evaluated in adult patients with advanced solid tumors in an intravenous dose escalation Phase 1 study
- GEN2 is well-tolerated, with no Dose Limiting Toxicity or treatment-related discontinuations
- Dose dependent increases in immunocytokines and vector persistence in peripheral blood mononuclear cells at the two highest dose levels support GEN2 transgene expression and mechanism of action
SAN MARINO, Calif., Nov. 07, 2025 (GLOBE NEWSWIRE) -- GenVivo, Inc., a clinical-stage biopharmaceutical company pioneering a patented, off-the-shelf vector platform to combat cancer by activating the patient’s immune system against the entire repertoire of their own tumor antigens, announces the presentation of GEN2 Phase 1 clinical trial results in adult patients with advanced solid tumors (NCT06391918), at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 7-9, in National Harbor, MD.
Poster
- Abstract Title: “Phase 1 Study of GEN2, A Personalizing Systemic Cancer Immunotherapy, in Adult Patients with Advanced Solid Tumor Malignancies”
- Session Date and Time for Poster Presentation: Friday, Nov. 7, 2025
- Abstract Number: 573
- Presenter: Anthony El-Khoueiry, MD
GEN2, an off-the-shelf non-replicating mRNA vector, delivers two payload genes that provide dual-mechanisms of action: an enhanced prodrug-activator enzyme (HSV-eTK) and an immunostimulatory cytokine (GM-CSF). After valganciclovir (VGCV) prodrug administration, GEN2 triggers the local release of tumor-specific antigens (including neoantigens) to stimulate an immune response. This novel therapy enables faster treatment, as it does not require tumor biopsies or tumor-specific genomic sequencing to identify patient-specific neoantigens and create an individualized therapy prior to commencing treatment.
GEN2 was dosed intravenously (IV) across five dose levels (3.4 × 10⁶ to 2 × 10⁸ TU/kg) in combination with VGCV in 23 patients in this Phase 1 dose-escalation trial. GEN2 was administered on Days 1, 3, and 8, followed by VGCV on days 12 to 21 during the four-week cycle. GEN2 demonstrated tolerability and minimal toxicity, with no Dose Limiting Toxicity (DLT) observed and no treatment-related discontinuations. Treatment-related adverse events included diarrhea (22%), nausea (17%), vomiting and fatigue (13% each), all Grade 1–2. Stable disease >24 weeks was observed.
GEN2’s mechanism of action was supported through pharmacodynamic and biomarker data (including cytokines and other plasma proteins). Dose-dependent increases in GM-CSF were observed with intravenous GEN2 administration. Levels of IL-2, IFNγ, CCL4 and CCL3 also showed increasing trends, further indicating GEN2 induced biological activity. Vector persistence in peripheral blood mononuclear cells (PBMCs) confirmed GEN2’s transgene expression; elimination of the signal after VGCV administration demonstrated the effectiveness of the pro-drug activated enzyme, HSV-eTK.
Cycle 2 Day 1 data showed a lower exposure than for Cycle 1 at the higher dose levels. This was coincident with the development of neutralizing antibodies; alternate dosing schedules, and premedication strategies to mitigate neutralizing antibody generation are under evaluation. A parallel intratumoral (IT) cohort continues in cutaneous malignancies.
“GEN2 represents a unique systemic treatment modality employing an ‘off-the-shelf’ gene delivery vector that exerts immunotherapeutic effects through multiple mechanisms of action,” said Dr. Anthony El-Khoueiry, Chief of the Section of Developmental Therapeutics and Verna R. Richter Chair in Cancer Research at the University of Southern California (USC) Norris Comprehensive Cancer Center in Los Angeles, CA. “These data verified GEN2's gene transduction, consistent with its putative mechanism of action, resulting in increased cytokine and immunomodulatory protein biomarkers, and creating the potential to promote an anti-tumor immune response.”
“The GEN2’s pharmacokinetic, pharmacodynamic, and safety data together with the demonstration of the effectiveness of the ‘off’-switch provide clinical validation of GenVivo’s G-VolveTM vector platform, the basis for GEN2,” said Dr. Robert G. Johnson, Chief Operating Officer of GenVivo, Inc. “The GEN2 data provide a solid foundation for advancing our G-VolveTM platform, including IL-12 and in vivo CAR-T vector programs.”
GEN2’s IV administration represents a major advancement over alternative therapies limited by IT or Intralesional (IL) approaches, as local administration is usually restricted to readily accessible tumors. While clinical trials of oncolytic viruses or replication-deficient vectors have demonstrated encouraging results in skin, bladder, prostate, pancreatic, and lung cancers (sometimes showing abscopal effects in both injected and non-injected tumors), there are practical limitations to IT or IL administration. By contrast, GEN2’s IV administration enables treatment of advanced disease with distant metastases.
About GenVivo
GenVivo (GVO) is a private, vertically integrated, clinical-stage biotechnology company founded to develop innovative gene delivery and immune stimulation therapies, which activate the patient’s immune system to treat cancer and autoimmune disease. GenVivo is committed to developing and manufacturing products that are rapidly deployed, and easily administered, personalizing, and yet off-the-shelf, with the goal of increasing cancer patient survival and improving quality of life for them and patients with autoimmune disease. GEN2, GVO’s first clinical candidate, is currently in a Phase 1 clinical trial in the US (NCT06391918). GenVivo’s pre-clinical pipeline includes GEN-1013, an IL-12 encoding therapy, and an in vivo CAR-T vector program.
For more information, visit https://genvivoinc.com/
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Contact Brian Korb Managing Director Brian.korb@partners.com Victor Constantinescu Head of Business Development BD@genvivoinc.com 626-768-5162
