KaliVir Immunotherapeutics Announces Clinical Trial Collaboration and Supply Agreement with Roche to Evaluate VET3-TGI in Combination with Atezolizumab (Tecentriq®) in Advanced Solid Tumors
KaliVir Immunotherapeutics, Inc., a clinical-stage biotechnology company advancing next-generation, multi-mechanistic oncolytic immunotherapies, today announced a significant clinical trial collaboration and supply agreement with Roche. The partnership will evaluate VET3-TGI—KaliVir’s lead oncolytic immunotherapy candidate created through its proprietary Vaccinia Enhanced Template (VET™) platform—in combination with Roche’s anti-PD-L1 immune checkpoint inhibitor, atezolizumab (Tecentriq®). This collaboration marks a major step forward in KaliVir’s strategy to explore novel immuno-oncology combinations capable of generating more durable, deep, and broad clinical responses in patients with hard-to-treat cancers.
Under the agreement, Roche will provide atezolizumab for use across multiple dosing cohorts within the STEALTH-001 Phase 1a/1b clinical trial (NCT06444815). The ongoing study is designed to evaluate VET3-TGI both as a monotherapy and, through this collaboration, in combination with an established checkpoint inhibitor in patients with advanced or metastatic solid tumors. The supply agreement enables the expansion of the combination-therapy arm, giving KaliVir the opportunity to thoroughly investigate the synergistic potential of combining an engineered oncolytic virus with a PD-L1 inhibitor.
Advancing a New Therapeutic Paradigm in Oncolytic Immunotherapy
VET3-TGI represents a next-generation approach to oncolytic virotherapy. Built on KaliVir’s Roche proprietary VET™ platform, VET3-TGI is designed to selectively infect and replicate within tumor cells, leading to the direct destruction of malignant tissue while simultaneously turning the tumor into a hub for immune activation. The therapeutic incorporates a dual-mechanistic payload engineered to overcome two major barriers in immunotherapy: inadequate immune stimulation and immunosuppression within the tumor microenvironment (TME).
VET3-TGI encodes interleukin-12 (IL-12), a cytokine known for its powerful ability to activate T cells and natural killer (NK) cells, alongside a transforming growth factor-beta (TGF-β) inhibitor, intended to disrupt key immunosuppressive signaling pathways. Together, these mechanisms aim to recondition the TME from an immune-excluded or immune-suppressive state into one that is more favorable for effective anti-tumor responses.
When combined with atezolizumab, which blocks the PD-L1 immune checkpoint pathway to prevent tumor-mediated immune evasion, the Roche therapeutic strategy seeks to not only increase tumor-infiltrating immune cells but also enhance their ability to function effectively. This multi-layered approach has the potential to convert non-responsive or weakly responsive tumor types into settings where checkpoint inhibitors may demonstrate enhanced activity.
Leadership Perspective and Strategic Value of the Collaboration
“This clinical collaboration with Roche allows us to build on promising clinical and preclinical data by expanding the evaluation of VET3-TGI beyond monotherapy and into combination therapy with an established checkpoint inhibitor,” said Helena Chaye, CEO of KaliVir Roche Immunotherapeutics. “Partnering with Roche, a global leader in oncology, represents an important step toward advancing innovative therapeutic strategies. We are excited about the opportunity to explore the full potential of this novel combination for patients with advanced solid tumors.”
Chaye emphasized that the agreement not only validates the scientific promise of VET3-TGI but also strengthens KaliVir’s footprint in the immuno-oncology landscape. The collaboration reflects the growing industry interest in combination regimens leveraging oncolytic viruses to potentiate existing immunotherapies. By combining complementary mechanisms of action—viral oncolysis, immune stimulation, TME remodeling, and checkpoint blockade—the partnership aims to unlock broader clinical benefit in tumor types where immunotherapy alone has shown limited success.
About VET3-TGI: A Novel Multi-Mechanistic Oncolytic Immunotherapy
VET3-TGI is KaliVir’s most advanced clinical candidate and exemplifies the company’s innovations within the vaccinia virus platform. The VET™ platform allows KaliVir to introduce multiple, precisely engineered genetic modifications, optimizing viral replication, tumor selectivity, systemic delivery, and immune activation. The enhancements incorporated into VET3-TGI include:
- Selective Tumor Replication: Genetic alterations allow the virus to preferentially replicate in tumor cells while minimizing activity in normal tissues.
- IL-12 Expression: Controlled expression of IL-12 promotes potent local immune activation without the toxicities associated with systemic IL-12 exposure.
- TGF-β Inhibition: Local inhibition of TGF-β helps counteract one of the most powerful immunosuppressive pathways present in the TME.
- Enhanced Systemic Delivery: Optimizations in the viral backbone allow for both intratumoral (IT) and intravenous (IV) administration, with the latter enabling access to widespread or inaccessible tumor lesions.
Through these features, VET3-TGI aims to initiate a robust multi-faceted anti-tumor response: direct cancer cell destruction, enhanced antigen release, and improved infiltration and activation of immune cells capable of targeting both injected and distant metastatic sites.
STEALTH-001 Study Overview
The STEALTH-001 clinical trial is a first-in-human, open-label, multicenter Phase 1a/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of VET3-TGI. The study includes both dose-escalation and dose-expansion phases and enrolls adult patients with histologically confirmed, advanced, unresectable, or metastatic solid tumors that are refractory to standard therapy or have no available curative treatment options.
The STEALTH-001 trial is evaluating:
- Intratumoral administration of VET3-TGI, providing localized viral delivery directly into the tumor mass
- Intravenous administration, enabling treatment of deep-seated or disseminated disease that cannot be easily accessed by injection
- VET3-TGI as a monotherapy, assessing its independent anti-tumor activity
- VET3-TGI in combination with atezolizumab, supported by the newly announced collaboration with Roche
Preclinical studies demonstrated that VET3-TGI has potent Roche oncolytic activity and can induce systemic anti-tumor immune responses capable of targeting both injected and uninjected lesions. Early clinical findings have supported the tolerability profile expected from the selectively replicating vaccinia backbone, with dose escalation progressing as planned.
The addition of the combination arm with atezolizumab will allow the trial to explore whether the TME reprogramming and immune-priming effects of VET3-TGI can enhance sensitivity to checkpoint blockade. Observing responses in traditionally checkpoint-refractory tumors—such as certain gastrointestinal, pancreatic, or mucinous cancers—would be a particularly meaningful signal of therapeutic synergy.
A Growing Role for Oncolytic Immunotherapies
Oncolytic viruses have emerged as one of the most promising Roche modalities in immuno-oncology due to their ability to deliver multifaceted therapeutic activity. Unlike traditional cytotoxic therapies, oncolytic viruses can simultaneously:
- Destroy tumor cells through viral replication
- Release tumor antigens that attract and activate immune cells
- Deliver immune-modulating transgenes directly into the tumor
- Recondition the TME to enhance responsiveness to other therapies
The vaccinia virus, in particular, offers unique advantages including large genomic capacity, systemic deliverability, rapid replication, and an established safety profile. KaliVir’s VET™ platform builds on decades of vaccinia research while introducing modern genetic engineering capabilities to unlock new therapeutic potential.
Combining Roche oncolytic viruses with checkpoint inhibitors is increasingly viewed as a rational strategy to enhance clinical efficacy. While checkpoint inhibitors have transformed cancer treatment, the majority of patients do not achieve durable responses due to insufficient pre-existing immune priming or deeply immunosuppressive TMEs. Oncolytic viruses are uniquely positioned to initiate or intensify tumor inflammation, converting “cold” tumors into “hot” ones—creating an environment where checkpoint inhibitors can be more effective.
About KaliVir Immunotherapeutics, Inc.
KaliVir Immunotherapeutics is a clinical-stage biotechnology company pioneering the development of systemic, next-generation oncolytic immunotherapies. The company’s foundation lies in its proprietary VET™ (Vaccinia Enhanced Template) platform, which enables the engineering of optimized oncolytic vaccinia backbones tailored for potent, systemic anti-tumor activity. Through strategic design of viral genomes, KaliVir integrates multiple genetic modifications to enhance tumor selectivity, immune activation, and therapeutic payload delivery.
The company’s pipeline includes a range of VET-based candidates engineered for different tumor types and therapeutic strategies, all built upon a platform capable of delivering combinations of cytokines, immune checkpoint inhibitors, and TME-modifying agents. KaliVir’s mission is to leverage the full potential of oncolytic immunotherapy to provide transformative options for patients with advanced cancers who currently have limited treatment alternatives.
With VET3-TGI advancing through clinical development and new collaborations underway—including the newly announced partnership with Roche—KaliVir continues to solidify its position as a leading innovator in the rapidly advancing field of viral immunotherapy.
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