Abstract 794P
Background
Cutaneous basal cell carcinomas (BCCs) carry a high mutational burden and are accompanied by a regulatory T-cell-rich tumor microenvironment, which makes them an attractive target for oncolytic virotherapy. This is the first clinical trial to report data on the efficacy of Talimogene laherparepvec (T-VEC) in BCCs. We hypothesized that neoadjuvant treatment with T-VEC can reduce the size of difficult to resect primary BCCs to allow surgery without skin grafts or skin flaps.
Methods
In this exploratory phase II study, 18 patients (11 female, 7 male) with a difficult to resect BCC, defined as requiring a reconstructive skin flap or skin graft for wound closure, were included. The patients’ median age was 76 years (range 51-94 years). T-VEC was administered intratumorally, according to the melanoma treatment schedule, with a total of 6 cycles (13 weeks). Pre- and posttreatment tumor samples were analyzed using multiplex immunofluorescence (mIF) and changes in immune and non-immune cells contributing to the tumor microenvironment were quantified.
Results
Between January 2020 and January 2022, 18 patients started therapy. 17 were included for the final analysis. Treatment was prematurely discontinued in 1 patient after 2 cycles because of treatment related fever, Grade 2 (CTCAE Version 5.0). The median follow-up was 15.9 months (range: 0.3-28.7 months). The mean tumor area reduction was 48.7%, respectively. The primary endpoint was reached since 9 (52.9%) out of 17 patients underwent surgery without a skin graft or skin flap. 6 patients (35.3%) had a CR, 4 (23.5 %) a PR, 7 (41.2%) a SD, whereas no patient showed a PD prior to surgery. T-VEC reprogrammed the immune cell landscape of BCCs, with an increasing number of CD8+ T-cells, CD79+ plasma cells and a decreasing number of CD4+FOXP3+ regulatory T-cells and CD68+ myeloid cells. The safety analysis set included all patients, that at least received one dose of T-VEC. 15 (83.3%) of 18 patients developed treatment related Grade 1 or 2 AEs. None of the patients had serious adverse events (SAEs). No tumor recurrence occurred.
Conclusions
Neoadjuvant treatment with T-VEC was well tolerated and showed high activity in difficult to resect primary BCC.
Clinical trial identification
EudraCT number 2018-002165-19.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Amgen.
Disclosure
J.M. Ressler: Financial Interests, Invited Speaker: BMS, Novartis, Amgen; Financial Interests, Training: Novartis. T. Silly: Financial Interests, Invited Speaker: Novartis. C. Hoeller: Financial Interests, Personal, Advisory Board: Amgen, BMS, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Novartis, Pierre Fabre, Sanofi, Amgen; Financial Interests, Personal, Principal Investigator: Amgen, BMS, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche; Non-Financial Interests, Member: EORTC Melanoma Group, EADO. All other authors have declared no conflicts of interest.