1138P - Intralesional administration of L19IL2/L19TNF in difficult-to-treat non-melanoma skin cancer shows a favorable safety profile and preliminary clinical activity

Background

Non-melanoma skin cancers (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are the most common forms of skin cancer, with a rising incidence due to deficient sun protection and growing life expectancy. Treatment options include surgery, radiotherapy, immunotherapy, targeted therapy, or chemotherapy. Surgery typically offers high cure rates; however, surgery's suitability and/or effectiveness in certain patients (pts) may be limited by disease factors (location, functional and cosmetic impairment) or pts factors (age, comorbidities, personal preferences). Initial intralesional treatment with immunostimulatory drugs may be another therapeutic approach, potentially curing NMSC or making surgery less invasive. Here we investigate a combination of 2 immune cytokines (Bifikafusp alfa (L19IL2) and Onfekafusp alfa (L19TNF) targeting the extra domain B of fibronectin (EDB) for selective delivery of immunostimulatory payloads to the tumor site. EDB is virtually absent in healthy adult tissues but highly expressed in tumors, including NMSC.

Methods

In a single-arm, ongoing, phase II study (NCT04362722), pts with locally advanced, non-metastatic, node-negative, single or multifocal NMSC, not eligible for surgery or radiotherapy or who refuse it, are treated with 4 weekly intratumoral administrations of L19IL2/IL19TNF. 14 pts (11 BCC and 3 cSCC) have been treated and are evaluable for safety and efficacy.

Results

Administration of L19IL2/L19TNF was well tolerated with no grade 4-5 adverse events (AE). The most common treatment-related AEs were flu-like symptoms (36.4%), pyrexia (27.3%), face edema, chills, and injection site reaction (13.6%), all transient, managed with symptomatic therapy. In BCC cohort, ORR was assessed on day 36 with a 27.3% RR. In the follow-up, 5/11pts achieved pathological complete response (pCR) with an average time to pCR of 66 days from the first administration. In the 3 SCC pts, ORR was 33.3 % with 1 pCR.

Conclusions

The tolerable safety profile of L19IL2/L19TNF and the results obtained in pts with NMSC justify further exploring the potential of intralesional administration of immunostimulatory drugs in this setting.

Clinical trial identification

EudraCT 2020-003299-42, NCT 04362722.

Editorial acknowledgement

Legal entity responsible for the study

Philogen SpA.

Funding

Philogen SpA.

Disclosure

L. Flatz: Financial Interests, Personal, Stocks or ownership: Hookipa Pharma; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: BMS, Novartis, Sanofi, Philogen; Financial Interests, Institutional, Research Funding: Hookipa Pharma; Financial Interests, Personal, Royalties: Hookipa Pharma. U. Leiter-Stoppke: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Sun Pharma, Allmiral Hermal, Sanofi; Financial Interests, Personal, Other, Travel Support: Sun Pharma; Financial Interests, Personal, Advisory Board: MSD, Novartis, Sun Pharma, Allmiral Hermal, Sanofi; Financial Interests, Personal, Member, Board member: ADO (DECOG). N. wagner: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre; Other, Personal and Institutional, Principal Investigator: Sanofi, Regeneron, Pierre Fabre, Philogen; Other, Personal, Member: SITC; Financial Interests, Personal, Other, Travel Support: Amgen. L. Nadal, E. Puca, G. Elia: Financial Interests, Personal, Officer, Employee: Philogen S.p.A. A. Covelli: Financial Interests, Personal, Other, Member of the Scientific Board: Cellestia Biotech AG, Basel, Italfarmaco S.p.A., Milano, Peptomyc S.L, Barcelona; Financial Interests, Personal, Officer, Chief Medical Officer: Philogen S.p.A., Siena. D. Neri: Financial Interests, Personal, Member of Board of Directors: Philogen S.p.A; Financial Interests, Personal, Stocks or ownership: Philogen S.p.A. C. Antonio: Financial Interests, Personal, Advisory Board: AbbVie, Sanofi, Eli Lilly, Philogen. T.M.S. Amaral: Financial Interests, Personal, Writing Engagement: CeCaVa; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pierre Fabre; Financial Interests, Institutional, Funding: Novartis, Neracare, Sanofi, Skyline-Dx; Financial Interests, Institutional, Research Grant: Novartis, iFIT; Financial Interests, Institutional, Local PI: IO Biotech, MSD, University Hospital, Essen, Roche; Financial Interests, Institutional, Coordinating PI: Unicancer; Non-Financial Interests, Member: Portuguese Society for Medical Oncology, ASCO; Other, Clinical expert: Infarmed. All other authors have declared no conflicts of interest.