Despite recent advances in therapeutic options for advanced melanoma patients, there is still an unmet medical need for melanoma patients with local recurrence, who are candidates for surgical resection of all metastases. These patients are at a high risk of further recurrences until the disease becomes inoperable (unresectable), or progresses to Stage IV (distant organ involvement), for which the prognosis is particularly grim.
NidlegyTM is a combination of the immunocytokines L19IL2 and L19TNF, which is being developed as intralesional treatment for patients with advanced locoregional melanoma and non-melanoma skin cancers. In preclinical melanoma tumor models, the combination of the two agents has shown striking anti-cancer responses achieving cures in all treated animals.
In a phase II clinical study conducted in stage III/IVM1a melanoma patients, NidlegyTM led to complete responses not only on the injected tumor lesions but also on the majority of non-injected lesions (proving the onset of a systemic immune response induced after the intralesional injection of the product).
In a phase III study in patients with locally advanced melanoma, intralesional administration of NidlegyTM followed by surgery demonstrated a statistically significant and clinically meaningful benefit in Progression Free Survival (PFS) compared to surgery alone. The results of this trial were presented at ASCO 2024. A Marketing Authorization Application has been submitted to EMA and a combination pack request for the use of NidlegyTM has been approved by EMA. Moreover, a second phase III trial in patients with locally advanced melanoma is running in the United States and in Europe.
In addition, Philogen has initiated a phase II clinical trial in the United States with NidlegyTM (intralesional) in combination with anti-PD-1 therapy (systemic) in patients that have progressed after immune checkpoint inhibitors.
Inspired by the performance of NidlegyTM in melanoma, Philogen is also running two phase II clinical programs to investigate the efficacy and safety of the product in injectable, locally-advanced basal cell carcinoma and in other non-melanoma skin cancers.
The program is partnered with SUN Pharmaceuticals for the treatment of skin cancers in Europe, Australia, and New Zealand.
ONGOING CLINICAL TRIALS
- Two randomized, controlled phase III registration trials for intralesional application of NidlegyTM as a neoadjuvant followed by surgery + eventual adjuvant treatments (standard of care) and compared to standard of care are currently ongoing in Europe (NCT02938299) and in the USA (NCT03567889) in patients with fully resectable stage IIIB/C melanoma.
- A phase II trial in non-melanoma skin cancer (i.e., high-risk patients with Basal Cell Carcinoma and Cutaneous Squamous-Cell Carcinoma) (NCT04362722).
ONGOING CLINICAL TRIALS
Melanoma
•A randomized, controlled Phase III registration trial in Europe for intralesional application of NidlegyTM in patients with fully resectable stage IIIB/C melanoma as a neoadjuvant followed by surgery + eventual adjuvant treatments (standard of care) and compared to standard of care has met the primary endpoint (NCT02938299, results published in Annals of Oncology). A similar randomized, controlled Phase III trial in the same patient population is currently ongoing in the USA and Europe (NCT03567889).
•A randomized, open-label, three-arm, parallel Phase II study in the United States is evaluating the efficacy of single agent L19IL2, single agent L19TNF, and the combination L19IL2+L19TNF (NidlegyTM) given concurrently with anti-PD1 therapy in patients with refractory unresectable stage III-IV melanoma (NCT06284590).
Non-Melanoma Skin Cancer
•Two exploratory Phase II trials for intratumoral NidlegyTM in non-melanoma skin cancers (i.e., high-risk patients with Basal Cell Carcinoma and other NMSCs) (NCT04362722; NCT05329792).
•A Phase II study for intratumoral NidlegyTM in Europe and in the United States in third-line patients with locally advanced Basal Cell Carcinoma (NCT07227870).
•A Phase II study for intratumoral NidlegyTM in Europe and in the United States for intralesional treatment of second-line patients with locally advanced cutaneous Squamous Cell Carcinoma (NCT07228442).
•A randomized, open-label, three-arm, parallel Phase II study in Europe and in the United States to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and the combination L19IL2 + L19TNF (NidlegyTM) in first-line patients with locally advanced Basal Cell Carcinoma (NCT07227350).
References
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