Abstract CT004: A single arm phase 2 study of TVEC in patients with invasive cutaneous SCC: A novel therapeutic approach for low risk tumors

Abstract Background: Immune recognition and cytotoxic responses play an important role in the pathogenesis and progression of cutaneous squamous cell carcinoma (cSCC). Talimogene laherparepvec (TVEC) is an HSV-1 oncolytic immunological agent FDA approved for the local treatment of unresectable recurrent melanoma. It is proposed that T-VEC directly destroys cancer cells, and induces production of GM-CSF to enhance systemic antitumor immune priming. This proposed mechanism of action supports the novel approach to implement TVEC in the management of cSCC, particularly, in patients with increased burden of primary tumors. Methods: Study subjects were Immunocompetent, ≥ 18 years of age, and diagnosed with at least one histologically confirmed primary low-risk cSCC according to the Brigham and Women staging system. Unresectable lesions or patients unable/unwilling to undergo standard of care treatment were eligible to participate. Study lesions included target lesions injected (TLIs) and target non-injected lesions (TNILs). TNILs were selected to evaluate for abscopal effect when feasible. The TLIs were treated according to TVEC FDA approved protocol and followed for 1yr after the 1st injection. The primary study endpoint was to evaluate the overall response rate, defined as the proportion of subjects who achieved complete response and partial response in the TLIs. Safety and adverse effect profile (AEs), duration of response, time to response, durable response rate, and time to progression, were the secondary endpoints. A Simon 2 stage design was used. Total sample size was calculated to be 20 subjects. A total of 11 subjects were recruited, due to the COVID-19 pandemic and 100% CR observed in the interim analysis. NCT 03714828. Results: The analysis was conducted after all 11 participants completed Visit 8 (230-271 days from study initiation). Conclusions: TVEC showed extremely impressive ORR for patients with cSCC with a 95. 8% CR for TLIs. AE profile of TVEC was mild and was well tolerated. Further studies evaluating the role of intralesional immunotherapy should be considered in patients with increased burden of cSCC. Table 1. summarizes the study results. For the primary endpoint 100% of participants achieved an overall response. Primary outcomes for patients (n = 11) Secondary outcomes for TLIs (n = 24) Time to response - days Mean ± standard deviation Median/Range (min, max) 41. 6 ± 24. 9 Time to response - days Mean ± standard deviation Median/Range (min, max) 48. 7 ± 29. 2 35/ (18 - 112) 35/ (18 - 112) Final response to TVEC - % Overall response rate (ORR) Partial response (PR) Complete response (CR) 100% (11/11) 9. 1% (1/11) Response to TVEC - Overall response rate (ORR) Partial response (PR) Complete response (CR) 100% (24/24) 90. 9% (10/11) 4. 2% (1/24) 95. 8% (23/24) Duration of response - days Mean ± standard deviation Median - Range (min, max) 206. 0 ± 26. 0 Duration of response - days Mean ± standard deviation Median - Range (min, max) 201. 4 ± 29. 6 212 (140 - 236) 209 (136 - 250) Durable response rate - % 90. 9% (10/11) Durable response rate - % 83. 3% (20/24) Secondary outcomes for TNILs (n = 2) Final response to TVEC - % 100% (2/2) Adverse Events NCI CTCAE (v. 4. 0) Event n (%) 95% CI Severity Mild (Grade 1) Moderate (Grade 2) Fatigue 5 (45. 5%) (16. 7%, 76. 6%) 4 (80%) 1 (20%) Flu-like symptoms 4 (36. 4%) (10. 9%, 69. 2%) 3 (75%) 1 (25%) Headache 2 (18. 2%) (2. 3%, 51. 7% 2 (100%) Citation Format: Clara Curiel-Lewandrowski, Delaney B. Stratton, Anngela C. Adams, Haiyan Cui, Denise Roe, Srinath Sundararajan. A single arm phase 2 study of TVEC in patients with invasive cutaneous SCC: A novel therapeutic approach for low risk tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT004.