Emerging intralesional therapies for BCC

Surgery is the first-line treatment for patients with basal cell carcinoma (BCC). However, intralesional injections are being explored as a treatment option to minimise the drawbacks of surgical intervention. Various approaches, including oncolytic viruses and fibronectin-targeting products, have shown promising results.

“The incidence rates of cutaneous BCC have doubled over the last 2 decades,” said Dr Antonio Cozzio (Kantonsspital St Gallen, Switzerland) [1]. “Moreover, cutaneous BCC has the highest mutational burden of all human cancers.” The current gold standard therapy for BCC is surgery, which has a recurrence risk of 2–10%. Although staging is not yet widely adopted in clinical practice, it is important because treatment algorithms are closely linked to the disease stage. Dr Cozzio highlighted the recent staging proposed by the European Association of Dermato-Oncology (EADO), which updated the high/moderate risk criteria for these tumours and divided BCC development across 4 stages [2]. For stage 1 tumours, standard surgery is the first-line treatment option, whereas 3D surgery or micrographically-controlled surgery is advised for patients with higher-risk tumours. “In cases involving multiple BCCs, locally advanced tumours, or metastatic cancer, a multidisciplinary tumour board should be consulted,” explained Dr Cozzio. Fortunately, such cases are rare.

Cryotherapy, CO₂ laser, imiquimod, 5-fluorouracil, and photodynamic therapy (PDT) are alternative treatment options for BCC, depending on the lesion thickness. “Cryotherapy has the best cost-effectiveness profile for superficial lesions,” added Dr Cozzio. For nodular BCC, imiquimod may be used, although surgery yields superior outcomes. For patients seeking non-surgical alternatives, combination therapies are available. For example, a triple approach consisting of CO₂ laser therapy, methyl aminolevulinate-PDT, and contact cryotherapy appears to be an effective option for nodular BCC.

Typical intralesional interventions include methotrexate, interferon, and electrochemotherapy plus bleomycin. Methotrexate has limited efficacy in BCC, while interferon offers better outcomes, with response rates ranging from 52% to 98% and excellent cosmetic results [3,4]. On the other hand, interferon is an expensive treatment, difficult to acquire, and commonly causes flu-like side effects. Electrochemotherapy plus bleomycin has demonstrated complete response (CR) rates between 86% and 100% after 1 or 2 treatments, and a sustained CR rate of 89.4% at 5 years of follow-up [5]. “The main disadvantage of this treatment is that about one-third of the patients cannot tolerate the procedure under local anaesthesia and require general sedation,” commented Dr Cozzio.

In recent years, immunotherapies have become available for patients with non-melanoma skin cancer. “The mutational burden is high in epithelial skin cancer and is correlated to the efficacy of anti-PD1 or anti-PD-L1 immunotherapies,” according to Dr Cozzio. “However, the overall response rate of the anti-PD1 immunotherapy cemiplimab is only 32.1% in stage 1a BCC when applied locally [6].” He further explained that this limited efficacy might be due to BCC being a cold tumour, lacking inflammation in the tumour microenvironment. “If we could turn the cold tumour environment into a hot one, the responses may be better,” argued Dr Cozzio. One strategy to achieve this is to inject oncolytic viruses into the tumour. T-VEC is an FDA-approved oncolytic virus that may be used in unresectable melanoma. Although data is limited for BCC, a phase 2 study in the BCC population delivered encouraging efficacy and safety results of T-VEC injections [7]. “The study also showed that the cold tumour environment turned into a hot one with this treatment,” highlighted Dr Cozzio. These findings support further investigation of this approach in BCC treatment.

Another innovative method under investigation is daromun, comprising 2 antibodies with different payloads (L19IL2 or L19TNFa), targeting a specific fibronectin splice variant called extra-domain B, which is only found in growing tumours and is involved in tissue angiogenesis. Currently, a phase 2 study, DUNCAN (NCT04362722), is evaluating this agent in patients with BCC and other non-melanoma skin cancers. Dr Cozzio elaborated on the design and preliminary results of the DUNCAN trial. This study included 72 participants with BCC and 22 participants with cutaneous squamous cell carcinoma. So far, the treatment is well tolerated, and only 3 treatment-related serious adverse events were reported: ulcers, erysipelas, and periorbital cellulitis. “There was no induction of autoimmune disease,” emphasised Dr Cozzio. The first 6 evaluated participants displayed complete remission [8]. “A phase 3 trial, further testing this option in patients with BCC, will be opened at the end of this year,” said Dr Cozzio.

In summary, although 2D or 3D surgery is still the first-line option for most patients with BCC, evidence indicates that intralesional injections may be efficacious and safe for this patient population. With ongoing and planned trials testing oncolytic virus injections and daromun injections in patients with BCC, conclusive evidence may be presented in the near future.

1. Cozzio A. Intralesional treatment options for cutaneous BCC: where are we? Dermatologendagen 2025, 10–11 April, Apeldoorn, the Netherlands.
2. Peris K, et al. Eur J Cancer. 2023;192:113254.
3. Edwards L, et al. Arch Dermatol, 126(8), 1029–1032.
4. Urosevic M, Dummer R. Cancer. 2002;94(2):477-485.
5. Hendel K, et al. J Eur Acad Dermatol Venereol. 2021;35(11):2208-2215.
6. Stratigos AJ, et al. J Am Acad Dermatol. 2024 Feb;90(2):414-418.
7. Ressler JM, et al. Nature Cancer. 2025;6:51-66.
8. Flatz L, et al. J Eur Acad Dermatol Venereol. 2025;39(2):e147-e149.

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Posted on 5 June 20255 June 2025