Safety and preliminary efficacy of a first-in-class DRIP inhibitor EN002 topical gel in non-melanoma skin cancer and actinic keratosis: An international phase I study

Summary: Background:<b> </b>EN002 is an anticancer compound developed based on the novel anticancer targets, DNA Replication-Initiation Proteins (DRIPs). It selectively induces apoptosis of cancer cells but not normal cells, and leads to >90% tumor remission in mouse xenograft models. Here we report the Phase I dose escalation study data of EN002 in non-melanoma skin cancer (NMSC) and precancerous lesions. Methods:<b> </b>Subjects, mostly with recurrent or relapsed cutaneous basal cell carcinoma (BCC), Bowen's disease (BD), cutaneous squamous cell carcinoma (cSCC), or actinic keratosis (AK) were treated topically with EN002, to evaluate the safety, PK and preliminary efficacy. A BOIN design was used for dose escalation from 0.008 to 0.12 mg/cm². Subjects were treated q2d for 24 days and followed-up for 28 days. Results:<b> </b>29 subjects completed the study, including 6 BCC, 1 cSCC, 6 BD and 16 AK cases in China and Australia. The adverse events (AEs) were Grades 1 and 2, without SAE or DLT. Treatment-related AEs were primarily local skin reactions, which were mild and transient. EN002 in subjects with NMSC had an objective response rate (ORR) of 62% (8/13) and disease control rate (DCR) of 100%. One case of invasive cSCC achieved PR at day 16. The ORR of BCC was 50% (3/6), while that in Australia was 75% (3/4). AKs were cleared to different degrees, from 0-100%. EN002 in most blood PK samples were very low and no increase in systemic exposure was observed with increasing dose. Conclusions: The phase 1 study provided preliminary clinical evidence of a favorable benefit-risk profile of a novel topical therapy for patients with naïve, recurrent or relapsed NMSC or AK, who represent unmet medical needs. In the ongoing Phase II study with expanded treatment duration, the first 4 enrolled patients all achieved 100% clearance in 9 weeks. Chun Liang^{1, 3}, Zijun Zhao², Jia Yan², Lan Zou³, Xiuli Wang² 1. Hong Kong University of Science and Technology, Hong Kong, China. 2. Shanghai Skin Disease Hospital; School of Medicine, Tongji University, Shanghai, China. 3. EnKang Pharmaceuticals (Guangzhou), Ltd., Guangzhou, China. Clinical Research: Interventional Research