Verrica Pharmaceuticals and Lytix Biopharma announced positive preliminary topline results from part 2 of a phase 2 clinical trial evaluating VP-315 (LTX-315) in patients with basal cell carcinoma. The data indicate that VP-315, a potential first-in-class oncolytic peptide, led to reductions in tumor size in a significant proportion of patients. This investigational agent is being developed as a non-surgical option for treating basal cell carcinoma by inducing lysis of intracellular organelles of tumor cells, thereby generating T-cell responses.
The open-label, multicenter, dose-escalation study (NCT05188729) enrolled patients with clinically suspected basal cell carcinoma. Key findings from the trial showed that among all patients treated with VP-315 (n = 93), 86% experienced a reduction in tumor size. Furthermore, complete histological clearance, defined as 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.
Safety Profile
Importantly, the trial reported no dose-limiting toxicities (DLTs) or serious treatment-related adverse effects (TRAEs) across all treated patients (n = 93). The TRAEs observed were limited to mild to moderate cutaneous reactions, which were anticipated.
Mechanism of Action and Potential
VP-315 is designed to be injected directly into basal cell carcinoma tumors. The agent's mechanism of action involves inducing lysis of intracellular organelles within tumor cells, which subsequently generates T-cell responses. This targeted approach offers a potential non-surgical alternative for patients with basal cell carcinoma.
Study Design
The phase 2 study consisted of two parts. Part 1 was a safety run-in, assessing escalating doses of VP-315. Part 2 involved multiple cohorts examining varying dosing schedules. Patients enrolled were 18 years or older with clinically suspected basal cell carcinoma, having at least one and up to five eligible lesions suitable for biopsy and excision. Lesions had to be between 0.5 cm and 2 cm in the longest diameter prior to punch biopsy, and diagnosed as nodular, micronodular, or superficial basal cell carcinoma.
Exclusion criteria included known or suspected systemic cancer, recent systemic chemotherapy, systemic immunotherapy, immunomodulators, or immunosuppressants. Patients with recurrent or previously treated lesions were also excluded, as were those with lesions located within 1 cm of the eyelids or lips, or on the hands, feet, ears, nose, or genitalia.
Dosing Regimens
Part 2 of the study evaluated several dosing schedules for VP-315, including:
- 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 primary endpoints in part 1 focused on the incidence of AEs, DLTs, and cutaneous reactions. In part 2, the primary endpoints were safety and the proportion of patients with cutaneous reactions. Secondary endpoints included the rate of patients with clinical clearance of treated lesions at excision, the proportion of patients with histological clearance, the rate of patients with abscopal effect at excision, and the mean estimated remaining tumor volume at excision.
Expert Commentary
Ted White, president and chief executive officer of Verrica Pharmaceuticals, stated, "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. 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."
Øystein Rekdal, PhD, chief executive officer of Lytix Biopharma, added, "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. It has the potential to be used either alone or in combination with surgery in early lines of treatment in this vast cancer population."
