Nidlegy (darleukin/fibromun) / Philogen, Sun Pharma - LARVOL DELTA

PH-ICKPD1-02/21: A phase 2 study of the efficacy of intratumorally administered L19IL2 or L19TNF or L19IL2/L19TNF, all in combination with systemic anti-PD1 Pembrolizumab, in stage III/IV unresectable melanoma patients with resistance to anti-PD1 checkpoint inhibitors (INTACT / MeRCI) (clinicaltrialsregister.eu) - P1/2 | N=65 | Not yet recruiting | Sponsor: Philogen S.p.A.

Checkpoint inhibition • New P1/2 trial • Melanoma • Oncology • Solid Tumor • BRAF

Intralesional L19IL2/L19TNF in high-risk lacSCC patients: results from the Phase II DUNCAN Trial Exploratory Cohort (EADO 2026) - No abstract available

Clinical • P2 data

Neo-DREAM: Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (clinicaltrials.gov) - P3 | N=248 | Recruiting | Sponsor: Philogen S.p.A. | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2018 ➔ Sep 2018

Enrollment open • Trial initiation date • Melanoma • Oncology • Solid Tumor

Neo-DREAM: Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (clinicaltrials.gov) - P3 | N=248 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P3 trial • Melanoma • Oncology • Solid Tumor

Neo-DREAM: Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (clinicaltrials.gov) - P3 | N=186 | Recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2024 ➔ Jun 2026 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Neo-DREAM: Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (clinicaltrials.gov) - P3 | N=186 | Recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2022 ➔ Dec 2024 | Trial primary completion date: Jun 2020 ➔ Jun 2023

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

L19IL2/TNF in patients with basal cell carcinoma (clinicaltrialsregister.eu) - P1/2 | N=53 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P1/2 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

PHL19IL2TNFCOMB04/24: L19IL2 or L19TNF or L19IL2/TNF in patients with basal cell carcinoma (BCC) (clinicaltrialsregister.eu) - P1/2 | N=85 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P1/2 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

L19IL2/L19TNF in patients with cutaneous squamous cell carcinoma (clinicaltrialsregister.eu) - P1/2 | N=54 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P1/2 trial • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Neoadjuvant Intralesional Targeted Immunocytokines (Daromun) in Stage III Melanoma. (PubMed, Ann Oncol) - "Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma. TRAEs were transient and manageable. Neoadjuvant daromun is a new therapeutic option for patients with stage III melanoma, including those with locoregional recurrence after surgery and previous adjuvant therapy."

Journal • Melanoma • Oncology • Solid Tumor

Phase 3 study (PIVOTAL) of neoadjuvant intralesional daromun vs. immediate surgery in fully resectable melanoma with regional skin and/or nodal metastases. (ASCO 2024) - P2, P3 | "The analysis of the primary efficacy endpoint RFS and of secondary endpoints DMFS, pCR and safety show that neoadjuvant Daromun is an effective and safe therapeutic option for resectable, locally advanced melanoma pts."

Clinical • Late-breaking abstract • P3 data • Surgery • Cutaneous Melanoma • Immunology • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Neoadjuvant Intralesional Daromun Improves Outcomes in Pretreated, Relapsed Stage III Melanoma — Subgroup Analysis of the Phase 3 PIVOTAL Study (SMR 2025) - No abstract available

Clinical • P3 data • Melanoma • Oncology • Solid Tumor

Neo-DREAM: Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (clinicaltrials.gov) - P3 | N=186 | Recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Jun 2026 ➔ Dec 2031 | Trial primary completion date: Jun 2024 ➔ Dec 2027

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

L19IL2/L19TNF in Patients With Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P2 trial • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

L19IL2 or L19TNF or L19IL2/TNF in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P2 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

L19IL2/TNF in Patients With Basal Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P2 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Favorable activity and safety of intralesional L19IL2/L19TNF in high-risk laBCC and lacSCC patients (ESMO 2025) - P2 | "Efficacy signals in laBCC and lacSCC support further evaluation in this setting. Daromun's safety profile remained consistent with previous data in melanoma."

Clinical • Late-breaking abstract • Melanoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Neoadjuvant immunotherapy with Daromun for cutaneous melanoma recurrence - first experience in the Early Access program (ADO 2025) - No abstract available

Clinical • Cutaneous Melanoma • Melanoma • Solid Tumor

Two case reports on the use of Daromun for the treatment of locally advanced, fully resectable stage III melanoma in clinical practice in Germany: two cases from the Compassionate Use Program (ADO 2025) - No abstract available

Case report • Clinical • Metastases • Melanoma • Solid Tumor

Efficay and Safety of DAROMUN on Patient Treated by Intralesionnal Injection: DAROMEL (clinicaltrials.gov) - P=N/A | N=70 | Not yet recruiting | Sponsor: Centre Hospitalier Universitaire de Nice

New trial • Melanoma • Oncology • Solid Tumor

Philogen Provides Update on Marketing Authorization Application for Nidlegy in th European Union (Philogen Press Release) - "Philogen S.p.A...announced the decision to voluntarily withdraw the application for marketing authorization to the European Medicines Agency (EMA) for Nidlegy, a biological investigational medicinal product which is intended to be used for the neoadjuvant treatment of adult patients with locally advanced fully resectable melanoma. The Marketing Authorization Application (MAA) for Nidlegy submitted in June 2024 was supported by data from PIVOTAL (NCT02938299), a randomized Phase 3 study in 256 patients with locally advanced fully resectable melanoma, in which Nidlegy reduced the risk of relapse or death by 41% compared to the control arm....The company's decision to withdraw the MAA was due to the timing of the availability of Chemistry Manufacturing and Controls (CMC) and additional clinical data to better characterize the benefit:risk profile in patients with locally advanced resectable melanoma."

European regulatory • Melanoma

New therapeutic approaches in the neoadjuvant/adjuvant treatment of melanoma (PubMed, Dermatologie (Heidelb)) - "The mRNA-based treatment combined with checkpoint inhibitors have the potential to induce long-term immune responses. The efficacy of LAG-3 inhibitors in the adjuvant setting is currently under evaluation in clinical studies. The immunocytokine treatment with daromun shows promising results in the neoadjuvant setting by stimulating both local and systemic immune responses. Future studies should focus on identifying optimal combinations of treatment to improve the long-term prognosis of patients."

Journal • Review • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • LAG3

Melanoma neoadjuvant treatment: review and update of recent trials. (PubMed, Expert Rev Anticancer Ther) - "The variety of regimens and dosing schedules investigated highlights the need for further research to determine the most appropriate treatments in this clinical setting. Advances in the study of biomarkers that can identify specific subgroups of patients will guide future research in this field."

IO biomarker • Journal • Review • Melanoma • Oncology • Solid Tumor

Topical and Intralesional Treatments for Skin Metastases and Locoregionally Advanced Melanoma. (PubMed, Cancers (Basel)) - "Diphenciprone, imiquimod and 5-florouracil were included as topical treatments and bacillus Calmette-Guerin, interleukin 2, rose bengal, talimogene laherparepvec and electrochemotherapy were included as intralesional treatments. Brief comments on other alternatives in development such as interferon-alpha, interleukin-12, ipilimumab and intralesional daromun are presented...It has also been described in a few papers that non-injected lesions may respond after the application of a local therapy in distant skin-metastases. Many of these intralesional treatments are being combined in different investigations with systemic immunotherapies, with the aim of obtaining synergic responses in those patients with refractory disease."

Journal • Review • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • IL12A • IL2

INTACT: Study of the Efficacy of Intratumoral L19IL2 or L19TNF or L19IL2/L19TNF, in Combination with Pembrolizumab, in Unresectable Melanoma Patients (clinicaltrials.gov) - P2 | N=162 | Recruiting | Sponsor: Philogen S.p.A. | Active, not recruiting ➔ Recruiting | Initiation date: Dec 2023 ➔ Jul 2024

Checkpoint inhibition • Combination therapy • Enrollment open • Trial initiation date • Melanoma • Oncology • Solid Tumor