VCN-01 Demonstrates Early Efficacy, Safety in Pediatric Refractory Retinoblastoma

Treatment with the oncolytic adenovirus VCN-01 was safe and elicited early signs of antitumor activity in patients with intraocular retinoblastoma that was refractory to chemotherapy or radiotherapy, and for whom enucleation was the only recommended treatment, according to topline data from a single-center phase 1 trial (NCT03284268).¹

Findings showed that VCN-01 was well tolerated in evaluable patients (n = 9). The majority of treatment-related adverse effects (AEs) were grade 1 or 2. No dose-limiting toxicities were reported, and ocular or systemic toxicities were all grade 3 or lower. Investigators reported ocular inflammation and associated turbidity after VCN-01 injection. Inflammation was managed, and vitreous haze improved in some cases with the local and systemic administration of anti-inflammatory drugs.

Regarding efficacy, 4 patients experienced a response, which was characterized by unequivocal improvement in vitreous seed density. Additionally, 3 patients have avoided eye enucleation as of data cutoff, including 1 patient who retained their eye after 4 years of follow-up.

A review of the data by a study monitoring committee deemed the results from the trial positive.

“Results from the investigator-sponsored trial further validate VCN-01’s unique mechanism of action and therapeutic potential to improve patient outcomes in otherwise refractory cancers,” Steven A. Shallcross, chief executive officer of Theriva Biologics, stated in a news release. “We look forward to building on the encouraging safety profile aSteven A. Shallcross, chief executive officer of Theriva Biologicsnd antitumor activity, which further supports and informs the design of our proposed phase 2 clinical trial.”

VCN-01, a systemically administered oncolytic adenovirus, is intended to selectively and aggressively replicate within tumor cells and degrade the tumor stroma, which is a significant physical and immunosuppressive barrier to cancer treatment.

The phase 1, open-label, dose-escalation trial conducted at Sant Joan de Déu-Barcelona (SJD) Children’s Hospital in Spain evaluated the safety and activity of VCN-01 in patients between 1 and 12 years of age with retinoblastoma that is relapsed or refractory to chemotherapy or radiotherapy, and whose only recommended treatment is enucleation. Patients needed to have retinoblastoma with a somatic RB1 mutation and an active tumor in a single eye; or a germinal RB1 mutation with active tumor(s) in an eye, and a contralateral eye that is unaffected, enucleated, or without tumor activity. Other key inclusion criteria consisted of normal renal, hepatic, and bone marrow function.²

Patients were excluded if they had factors that require immediate enucleation of the affected eye, including glaucoma, rubeosis iridis, or anterior chamber involvement; comorbidities such as uncontrolled epilepsy with anticonvulsant treatment or cardiac disease not compensated by treatment; active infections; trilateral retinoblastoma; and extraocular spread.

VCN-01 was administered as 2 intravitreal injections 14 days apart at doses of 2 x 10⁹ vp per eye (n = 1) or 2 x 10¹⁰ vp per eye (n = 8).¹

The incidence of treatment-emergent AEs served as the primary end point. Secondary end points included overall response rate, immune response, and the presence of VCN-01 in blood samples, aqueous humor, and ocular surface and nasal swabs.²

“The monitoring committee determined that the trial results were positive, and therefore, Theriva will receive an exclusive, worldwide license, and related patents from SJD for the treatment of pediatric patients with advanced retinoblastoma,” Shallcross added in the news release.¹ “The positive completion of this trial is an important step in refining our clinical strategy for VCN-01 as an adjunct to chemotherapy to address the high unmet need in this underserved indication.”

References

1. Theriva Biologics announces positive topline data from investigator sponsored phase 1 trial of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma. News release. Theriva Biologics. April 23, 2024. Accessed April 23, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-positive-topline-data-from-investigator-sponsored-phase-1-trial-of-intravitreal-vcn-01-in-pediatric-patients-with-refractory-retinoblastoma/
2. Evaluate safety and the oncolitic adenovirus VCN-01 activity in patients with refractory retinoblastoma (RTB). ClinicalTrials.gov. Updated April 22, 2024. Accessed April 23, 2024. https://clinicaltrials.gov/study/NCT03284268