CR Achieved in All Patients With Cutaneous BCC Given High-Dose STP705

A small interfering RNA (siRNA) therapeutic agent used to treat patients with cutaneous basal cell carcinoma (BCC) led to a complete response (CR) in all patients in the highest-dose cohort of a clinical trial, according to a press release from Sirnaomics.¹

In a dose-escalation phase 2 trial (NCT04669808), all 5 patients with cutaneous BCC who received the 180-μg dose of STP705 had a CR. Additionally, they reported no adverse events (AEs) and no significant cutaneous skin reactions.

“Achieving a 100% CR is a clear indication that our treatment has the potential to be an alternative to those treatments currently available to patients, which involve surgical excision of lesions,” Michael Molyneaux, MD, executive director and chief medical officer of Sirnaomics, said in a statement. “To reduce the rate of scarring and achieve a superior cosmetic result compared to surgery could be a potential advantage for patients with BCC and other non-melanoma skin cancers.”

STP705 is composed of 2 siRNA nucleotides that target the expression of TGF-β1 and Cox-2 mRNA, respectively. The drug is intended to cause downregulation of the expression of these genes to inhibit tumor growth, providing an alternative to surgical excision or other invasive treatment of BCC.

The phase 2 open-label dose escalation study is designed to evaluate the efficacy, safety, and tolerability of 5 different dose levels of STP705. Patients with a histologically-confirmed BCC lesion with a minimum diameter of 0.5 cm and with a maximum diameter of 2.0 cm were enrolled. They could not have received prior treatment such as immunomodulators, certain topical agents, treatment with liquid nitrogen, surgical excision (excluding diagnostic incisional biopsy), or curettage 4 weeks prior to the screening visit.

Patients received injections once weekly for 6 weeks. The primary end point was the proportion of patients with histological clearance of the treated lesion in a timeframe of 6 weeks, and a secondary end point was the change in clinical diameter in this timeframe. The investigators also aimed to determine the safe and effective dose of STP705.

Previous interim analysis of cohorts that received lower doses of STP705 were reported in February 2022.² Three dose escalation cohorts received 30 µg, 60 µg, and 90 µg doses. One patient out of 5 in the 30-µg cohort had a CR, while there were 3 CRs out of 5 in both the 60 µg and 90 µg cohorts. The 120-µg cohort had no reported data at this time or previously.

“The latest results from the phase 2 clinical study of STP705 for BCC treatment, showing an incredible efficacy without any drug-related AEs and serious AEs, further validated the broad potential of this drug candidate for treatment of non-melanoma skin cancers and beyond,” Patrick Lu, PhD, founder, chairman of the board, executive director, president, and CEO of Sirnaomics, said in a statement.¹

STP705 is being investigated in multiple clinical trials including a phase 1/2 trial [NCT04293679] for cutaneous squamous cell carcinoma in situ [isSCC], where it demonstrated strong efficacy with 19 out of 25 patients showing complete histological clearance.³ Another trial (NCT05421013) is investigating STP705 for facial isSCC. It is also being investigated outside of skin cancer in a trial (NCT04676633) of patients with cholangiocarcinoma and other disease types.¹

“Based on the successes of both BCC and isSCC clinical studies, Sirnaomics is spearheading the development of the novel polypeptide-based siRNA therapeutics for various types of cancers,” Lu concluded.

_References:

_{1. Sirnaomics achieves 100% complete response in phase ii clinical trial of STP705 for treatment of cutaneous basal cell carcinoma. Sirnaomics. August 29, 2022. Accessed August 30, 2022. https://bit.ly/3TwUKUK}

_{2. Sirnaomics announces interim data from phase ii clinical trial of STP705 for treatment of cutaneous basal cell carcinoma. Sirnaomics. February 23, 2022. Accessed August 30, 2022. https://bit.ly/3PZCsYX}

_{3. Nestor M, Berman B, Lu P, Molyneaux M. Safety and efficacy of TGF-β1/COX-2 silencing therapeutic in adults with cutaneous squamous cell carcinoma in situ. J Drugs Dermatol. 2022;21(5):472-477. doi:10.36849/JDD.6384}