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

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

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

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

Phase 3 study (PIVOTAL) of neoadjuvant intralesional daromun compared to immediate surgery in fully resectable melanoma with regional and/or lymph node metastases (JDP 2024) - No abstract available

Clinical • P3 data • Surgery • Melanoma • Oncology • Solid Tumor

Preliminary biomarker analysis in the Phase 3 PIVOTAL study: Evidence of the mechanism of action of Daromun in melanoma (ADO 2024) - P3 | "The H&E/IHC results showed a greater amount of TILs and a statistically significant higher influx in tumors of CD8+ T cells in Daromun-treated pts as compared to controls (unpaired t-test p < 0.0001). To a lesser extent, also CD4+ T cells were increased (p < 0.015). FACS analysis of PBMCs revealed a transient modest increase of Tregs and a trend to decrease of MDSCs in Daromun treated pts."

Biomarker • P3 data • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IL2RA

A post-hoc analysis of patients (pts) treated on Phase 3 PIVOTAL trial of neoadjuvant intralesional Daromun vs upfront surgery in stage 3, surgically resectable, advanced melanoma (SMR 2024) - No abstract available

Clinical • Late-breaking abstract • Metastases • P3 data • Retrospective data • Surgery • Melanoma • Oncology • Solid Tumor

Antibodies to watch in 2024. (PubMed, MAbs) - "In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi))...These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa)...Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Neoadjuvant L19IL2/L19TNF- Pivotal Study (clinicaltrials.gov) - P3 | N=214 | Active, not recruiting | Sponsor: Philogen S.p.A. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Dec 2028

Enrollment closed • Surgery • Trial completion date • Melanoma • Oncology • Solid Tumor • BRAF

Preliminary biomarker analysis in the phase III PIVOTAL study: Evidence for the mechanism of action of daromun in melanoma (ESMO 2024) - P3 | "An increase in absolute amount and changes in the abundance of TILs and PBMCs subpopulations provide a rationale for the systemic anti-tumor immune response, indicated by a 40% reduction of the risk of distant relapse in the Daromun arm. These results will be discussed, also in relationship to prior treatment with systemic therapies or to post-surgery treatment with adjuvant therapy."

Biomarker • P3 data • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IL2RA

Intratumoral administration of daromun in non-melanoma skin cancer: Preliminary results from a phase 2 non-randomized controlled trial. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Journal • P2 data • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor

Phase 3 Study (PIVOTAL) of Neoadjuvant Intralesional Daromun vs. Immediate Surgery in Fully Resectable Melanoma With Regional Skin and/or Nodal Metastases (OncLive) - "PIVOTAL (NCT02938299) is an open label, randomized, multicenter, phase 3 trial evaluating Daromun as a neoadjuvant intralesional therapy for resectable, locally advanced Stage III melanoma."

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Intralesional administration of L19IL2/L19TNF in high-risk locally advanced basal cell carcinoma or cutaneous squamous cell carcinoma. (ASCO 2024) - P2 | "Here, we investigate a combination of two immunocytokines (Bifikafusp alfa (L19IL2) and Onfekafusp alfa (L19TNF)) targeting the extradomain B of fibronectin (EDB) for the treatment of high-risk locally advanced BCC and cSCC. The first part of the trial has been completed with 28 laBCC pts and 12 lacSCC pts evaluable for safety and efficacy. The pre-specified activity goal for the first stage of accrual was met, and the second stage of accrual began in September 2023, with a total of 39 BCC and 18 cSCC pts enrolled so far."

Metastases • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • EDB-FN

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

Sun Pharma, Philogen seek European market access for melanoma drug Nidlegy (The Hindu Business Line) - "Sun Pharmaceutical Industries Limited and Philogen SpA announced they have submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for Nidlegy, an investigational treatment for locally advanced, fully resectable melanoma in the neoadjuvant setting. The submission is based on clinical data from phase 3 pivotal study and phase 2 trial. The approval would grant marketing authorisation for Nidlegy, an immunocytokine product."

EMA filing • Melanoma • Oncology • Skin Cancer • Solid Tumor

Neoadjuvant L19IL2/L19TNF- Pivotal Study (clinicaltrials.gov) - P3 | N=214 | Recruiting | Sponsor: Philogen S.p.A. | Trial primary completion date: Dec 2023 ➔ Oct 2024

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