VAX014 Demonstrates Safety, Early Signs of Immune-Mediated Activity in Advanced Solid Tumors

Findings from the dose-escalation segment of an ongoing, multicenter phase 1 trial (NCT05901285) showed that VAX014, a first-in-class, pan-tumor targeted oncolytic immunotherapy, was well tolerated as monotherapy and showed strong signs of immune-mediated antitumor activity in both injected and non-injected lesions in heavily pretreated patients with advanced solid tumors.¹

Subsequently, Vaxiion Therapeutics announced the initiation of the phase 1b dose expansion portion of the study, where investigators will further evaluate the safety and efficacy of VAX014 in combination with investigator’s choice of pembrolizumab (Keytruda) or nivolumab (Opdivo) in patients with solid tumors that have progressed on prior PD-1 blockade.

VAX014 is a novel bacterial minicell-based therapy specifically designed for optimal activity in STING– and RIG-I–positive tumors, aiming to overcome biological limitations seen with previously developed oncolytic virus–based therapies. Provided as a sterile product, VAX014 eliminates the need for BSL-2 biocontainment, potentially broadening patient access compared with conventional oncolytic virus treatments.

In the dose-expansion portion of the phase 1 study, 18 heavily pretreated patients with solid tumors were treated with VAX014 across 5 dose levels. The first 9 patients received injections into a single tumor at a fixed dose volume, and the last 9 were permitted to have multiple lesions injected.

“The monotherapy data with VAX014 is promising and I am eager to see how it performs in combination with pembrolizumab or nivolumab,” principal investigator Elizabeth Buchbinder, MD, of the Dana-Farber Cancer Institute in a news release. “Having a locally administered oncolytic immunotherapy option that doesn’t require special handling and biocontainment considerations has been really nice.”

Phase 1b Dose Expansion Overview

The ongoing phase 1b expansion study is now open and enrolling at 8 sites in the United States. This portion of the trial will employ an adaptive design to evaluate the safety and efficacy of VAX014 in combination with investigator’s choice of pembrolizumab or nivolumab in patients with solid tumors that have progressed following prior PD-1–directed checkpoint blockade. Based on current enrollment trends, up to 30 patients are expected to be enrolled over the next 12 months.

Patients 18 years of age or older with histologically confirmed, locally advanced or metastatic solid tumors that had progressed following at least one prior standard therapy—or who were intolerant to standard treatments with no other effective options—are eligible for enrollment.² Participants are required to have measurable disease by RECIST 1.1 criteria, an ECOG performance status of 0 to 2, and adequate hematologic, hepatic, renal, and coagulation function. Cohort-specific requirements include the presence of at least one injectable lesion, availability of tumor tissue for biopsy or archival analysis, and in the expansion phase, prior exposure and progression on PD-1–directed therapy with eligibility for nivolumab or pembrolizumab.

Key exclusions included recent anticancer therapy, untreated or unstable central nervous system metastases, severe active infection, need for systemic immunosuppression, active autoimmune disease, history of grade 4 toxicity to prior anti–PD-1 therapy, or clinically significant cardiovascular disease. Patients with active HIV, hepatitis B or C, tuberculosis, concurrent invasive malignancies, or those who were pregnant or breastfeeding were also excluded.

“We are happy to report the initiation of the dose expansion segment of this ongoing study and are encouraged by the safety and efficacy data as well as the positive investigator and patient feedback from the dose escalation study,” Matt Giacalone, chief executive officer of Vaxiion Therapeutics, stated in a news release.¹ “The phase 1b dose expansion will continue to build on our hypothesis that VAX014 facilitates development of robust antitumor T cell responses to potentiate the effectiveness of immune checkpoint blockade.”

References

1. Vaxiion Therapeutics announces completion of phase 1a dose escalation and initiation of a phase 1b dose expansion study for intralesional administration of vax014 in combination with pd-1 directed checkpoint blockade. News Release. Vaxiion Therapeutics. September 4, 2025. Accessed September 4, 2025. https://www.businesswire.com/news/home/20250903920007/en/Vaxiion-Therapeutics-Announces-Completion-of-Phase-1a-Dose-Escalation-and-Initiation-of-a-Phase-1b-Dose-Expansion-Study-for-Intralesional-Administration-of-VAX014-in-Combination-with-PD1-Directed-Checkpoint-Blockade
2. Phase 1 study of intratumoral administration of vax014 with expansion in combination with a checkpoint inhibitor in subjects with advanced solid tumors. Clinicaltrials.gov. Updated July 29, 2025. Accessed September 4, 2025. https://www.clinicaltrials.gov/study/NCT05901285