VP-315 Induces Reductions in Tumor Size in Basal Cell Carcinoma

Treatment with the potential first-in-class oncolytic peptide VP-315 (LTX-315) led to reductions in tumor size in patients with basal cell carcinoma, according to preliminary topline data from part 2 of a phase 2 trial (NCT05188729).^1,2

Findings showed that among all patients treated with VP-315 (n = 93), 86% experienced any reduction in tumor size. Additionally, complete histological clearance with no residual tumor cells was reported in 51% of lesions. In patients with remaining tumor (n = 90), the histological reduction in tumor size was 71%; data from the remaining 3 patients are pending.¹

Notably, no dose-limiting toxicities (DLTs) or serious treatment-related adverse effects (TRAEs) occurred in all treated patients (n = 93); TRAEs were comprised of anticipated mild to moderate cutaneous reactions.

“We believe the positive results from part 2 of the phase 2 study for VP-315 are a meaningful step forward in potentially providing [patients with] basal cell carcinoma with additional treatment options,” Ted White, president and chief executive officer of Verrica Pharmaceuticals, stated in a news release. “We are encouraged by our preliminary results, which we believe support the use of VP-315 as a first-line therapy for use in both a primary and neoadjuvant setting. We believe VP-315 has the potential to be a multi-billion dollar commercial opportunity for Verrica.”

VP-315 is intended to be injected directly into basal cell carcinoma tumors, potentially offering a non-surgical option for this patient population. The agent is designed to induce lysis of intracellular organelles of tumor cells, thereby generating T-cell responses.

The 2-part, open-label, multicenter, dose-escalation, proof-of-concept phase 2 study enrolled patients 18 years of age or older with clinically suspected basal cell carcinoma with at least 1 and up to 5 eligible lesions suitable for biopsy and excision. Patients were required to be willing to undergo surgical excision of target and nontarget lesions after study treatment, and they also needed to be willing to delay excision until an end-of-treatment visit.³

Basal cell carcinoma lesions needed to be at least 0.5 cm and no more than 2 cm in the longest diameter prior to punch biopsy. Patients were required to have a diagnosis of nodular, micronodular, or superficial basal cell carcinoma.

Patients were excluded if they had known or suspected systemic cancer; received systemic chemotherapy within 6 months of screening; received systemic immunotherapy, immunomodulators, or immunosuppressants with 12 weeks of screening; or had genetic or nevoid conditions.

Patients with recurrent or previously treated lesions were excluded. Other key exclusion criteria for lesions included a location within 1 cm of the eyelids or lips, or on the hands, feet, ears, nose, or genitalia; evidence of any other tumor on biopsy; an infiltrative, desmoplastic, sclerosing, or morpheaform subtype; and medium- to high-risk basal cell carcinomas.

Part 1 of the study consisted of a safety run-in, where VP-315 was administered at 2 mg on day 1, then escalated by 1 mg per day for up to 3 days per week. Patients were allowed to be treated for up to 2 weeks, and the maximum daily dose for part 1 was 8 mg.

Part 2 included multiple cohorts examining varying dosing schedules for VP-315:

• Cohort 1: 8 mg of VP-315 per day, except for a 4-mg dose on day 1 of week 1
• Cohort 2: 8 mg of VP-315 per day on all treatment days for up to 3 consecutive daily doses per week
• Cohort 4: 8 mg of VP-315 per day given on 2 consecutive days per week
• Cohort 5: 8 mg of VP-315 per day given on 3 consecutive days per week

The incidence of AEs, DLTs, and cutaneous reactions served as the primary end points in part 1. Safety and the proportion of patients with cutaneous reactions were the primary end points in part 2. Secondary end points in part 2 included the rate of patients with clinical clearance of treated lesions at excision; the proportion of patients with histological clears of treated lesions at excision; the rate of patients with abscopal effect at excision; the mean estimated remaining tumor volume at excision; the proportion of patients with Physician’s Global Assessment by scale; and pharmacokinetics.

“Together with our partner Verrica, we’re immensely proud of these results, showing that our lead drug candidate [VP-315] has a powerful anticancer effect in basal cell carcinoma,” Øystein Rekdal, PhD, chief executive officer of Lytix Biopharma, stated in a news release.² “It has the potential to be used either alone or in combination with surgery in early lines of treatment in this vast cancer population. This is a major leap for our unique treatment technology and an instrumental milestone in progressing [VP-315] towards commercialization.”

References

1. Verrica Pharmaceuticals announces positive preliminary topline results from part 2 of phase 2 clinical study of VP 315 an investigational oncolytic peptide based immunotherapy for the treatment of patients with basal cell carcinoma. News release. Verrica Pharmaceuticals. August 14, 2024. Accessed August 14, 2024. https://verrica.com/press_release/verrica-pharmaceuticals-announces-positive-preliminary-topline-results-from-part-2-of-phase-2-clinical-study-of-vp-315-an-investigational-oncolytic-peptide-based-immunotherapy-for-the-treatment-of-pat/
2. Lytix Biopharma AS: phase II preliminary results from skin cancer (BCC) clinical trial show an 86 percent overall reduction of tumor size, complete clearance in half of the patients and the potential to be utilized as a first-line therapy. News release. Lytix Biopharma. August 14, 2024. Accessed August 14, 2024. https://newsweb.oslobors.no/message/625105
3. Open-label proof of concept study of VP-315 in basal cell carcinoma. ClinicalTrials.gov. Updated August 1, 2023. Accessed August 14, 2024. https://clinicaltrials.gov/study/NCT0518872