Novel Intralesional Injection Achieves Complete Histological Clearance in Squamous Cell Carcinoma

Treatment withSTP705led to the achievement of complete histological clearance of squamous cell carcinoma in situ(isSCC) in a large proportion of patients, meeting the primary end point of the study, according to an interim analysis of the first 3 cohorts in an ongoing phase II clinical trial in patients with non-melanoma skin cancer announced by Sirnaomics Inc.

“The standard of care for the treatment of squamous cell carcinoma in situ is either surgical excision or destruction or radiation therapy. The advent of a non-surgical, scarless option using a simple series of injections with high cure rates will change the paradigm for the treatment of this common non-melanoma skin cancer,” Mark Nestor, MD, PhD, principal investigator and co-director of the Center for Clinical and Cosmetic Research, said in a statement.

The interim analysis is based on findings from the first 3 cohorts of patients who were treated with STP705 at doses of either 10 µg, 20 µg, or 30 µg. The primary end point of the trial is to evaluate complete histological clearance of treated isSCC lesion. The data cut-off date for this analysis was March 2, 2020.

Ten of 15 patients (66%) in the first 3 cohorts achieved complete histologically clearance. Three of 5 patients (60%) in the 2 cohorts of patients who received 10 µg and 20 µg of treatment achieved histological clearance of lesion compared with 4 of 5 patients (80%) who received 30 µg.

Key secondary safety end points also demonstrated promising results in the topline data. No treatment-related adverse events (AEs) occurred, as well as no serious AEs. In addition, no significant cutaneous skin reactions were observed.

Evaluation of 2 additional cohorts treating patients with 60 µg and 120 µgremainsongoing to define a clear therapeutic window for this agent.

The goal of this open-label dose escalation study is to evaluate the safety, tolerability, and efficacy of STP705 at multiple doses. The agent is administered as an intralesional injection.

Five dose-escalation cohorts will be evaluated in the study, including doses from 10 µg to 120 µg once a week for up to 6 weeks. Investigators plan to enroll 5 patients per dose level for a total of 25 patients.

STP705 is a small interfering RNA therapeutic which uses dual-targeted inhibitory property and polypeptide nanoparticle-enhanced delivery to knock down the TGF-β1 and COX-2 gene expression directly. The agent has received Investigational New Drug approvals in both the United States by the FDA, as well as in China, for the treatment of cholangiocarcinoma, non-melanoma skin cancer, and hypertrophic scar.

This agent has also previously been granted an Orphan Drug Designation for the treatment of patients with cholangiocarcinoma and primary sclerosing cholangitis. In preclinical animal models, STP705 has shown dramatic improvements in T-cell penetration into tumors in the liver either as a single-agent or in combination with an immune checkpoint inhibitor in a hepatocellular carcinoma model. Investigators hypothesize that this effect may improve other efficacies of immune checkpoint inhibition in addition to target the PD-1/PD-L1 axis.

isSCC is the earliest form of SCC, which is 1 of 2 major subtypes of non-melanoma skin cancer. The only current treatment option for this patient population remains surgery. However, surgery is associated with a significant recurrence rate, which leads to a major unmet need in this patient population.

To be included in this study, patients must have a histological diagnosis of no more than 6 months prior to the screening visit and a histological biopsy that removed ≤25% of the original area of the target lesion. Patients could not have any other dermatological disease in the isSCC target site or the surrounding area and must be willing to refrain from non-approved lotions/creams on the target site and surrounding area. Patients with a history of recurrence of the target lesion are not able to enter the study.

“It is very exciting to unveil the results from the interim analysis from our first clinical oncology study. This marks a significant milestone as evidenced by the large portion of the patients treated with STP705 for isSCC meeting the primary endpoint with a dose dependent manner. This interim clinical readout not only demonstrates the potential of RNAi therapeutics in the oncology application, but also illustrates the potential safety and efficacy of polypeptide nanoparticle delivery for siRNA therapeutics. In addition, the profound therapeutic efficacy further validates TGF-β1 and COX-2 as an important cancer drug target and our dual-targeting strategy for novel RNAi cancer therapeutics,” said Patrick Lu, PhD, president and chief executive officer of Sirnaomics, in a statement.

Reference:

Sirnaomics Announces Positive Topline Results from Interim Analysis of Ongoing Phase II Clinical Trial Evaluating STP705 in Cutaneous Squamous Cell Carcinoma in situ (isSCC) [news release] Gaithersburg, MD: Sirnaomics Inc.; April 8, 2020. https://bit.ly/2RscqlQ. Accessed April 9, 2020.