Abstract 1095TiP
Background
Daromun (Nidlegy®) is an immuno-oncology drug in clinical development for the treatment of melanoma and non-melanoma skin cancers (NMSC). The product, which is administered intralesionally, consists of two antibody-cytokine fusions as active principles (L19IL2 and L19TNF), which act synergistically to directly kill tumor cells while also inducing a systemic anti-tumor immune response. The drug is the first oncology product to receive EMA’s agreement for development as combination pack. Daromun is being investigated in two phase III studies in the neoadjuvant setting for fully resectable, locally advanced melanoma in EU and in the US. A phase II study in locally advanced NMSC (BCC and cSCC) has recently started in Europe. Finally, a phase II study in patients with unresectable melanoma, relapsed after or refractory to anti-PD1 treatment, is about to start in the US.
Trial design
The phase III neoadjuvant (NCT02938299 and NCT03567889) open label, randomized, controlled trials feature treatment with Daromun (13 Mio IU L19IL2 and 400 μg L19TNF) q1W over 4 weeks, followed by surgery and evtl. adjuvants decided by the treating physician (exptl. Arm). Patients randomized to the control arm receive the standard of care (surgery + adjuvants). Primary endpoint is RFS, secondary endpoints include OS, pathologic responses, safety. The EU study, ongoing at 20 centers in four countries, has enrolled more that ¾ of the expected sample size and has already passed the two interim analyses foreseen by the protocol, with the DSMB recommending prosecution of the study. The US trial has started later, is running at 5 clinical centers, while more centers are in the process of being opened. A phase II, open label study (NCT04362722) in 40 patients with localized, injectable BCC or cSCC is ongoing in Switzerland and expansion in other EU countries is planned. Patients receive L19IL2/L19TNF injections (6.5 Mio IU and 200 μg/dose, respectively) q1W over 4 weeks. Primary endpoint is ORR (CR + PR) at week 6 (RECIST 1.1). Encouraging results have been observed in the first treated patients. Finally a phase II, 3-arms controlled study in unresectable advanced melanoma patients resistant to anti-PD1 inhibitors is expected to start in q3 2021 in the US.
Clinical trial identification
NCT02938299, NCT03567889, NCT04362722.
Editorial acknowledgement
Legal entity responsible for the study
Philogen S.p.A.
Funding
Philogen S.p.A.
Disclosure
K.C. Kähler: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Sanofi Aventis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Philogen; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Other, Travel: Novartis; Financial Interests, Personal, Other, Travel: Sun Pharma; Financial Interests, Personal, Other, Travel: BMS; Financial Interests, Personal, Other, Travel: MSD. J.S. Zager: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Castle Biosciences; Financial Interests, Personal, Advisory Role: NeraCare; Financial Interests, Personal, Advisory Role: Delcath Systems; Financial Interests, Personal, Advisory Role: Philogen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sun Pharma; Financial Interests, Institutional, Research Grant: Castle Biosciences; Financial Interests, Institutional, Research Grant: Delcath Systems; Financial Interests, Institutional, Research Grant: Philogen; Financial Interests, Institutional, Research Grant: Provectus. G. Elia: Financial Interests, Personal, Full or part-time Employment: Philochem AG. D. Neri: Financial Interests, Personal, Ownership Interest: Philogen; Financial Interests, Personal, Member of the Board of Directors: Philogen.