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

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."

Video

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

INTACT/MeRCI: 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 | Active, not recruiting | Sponsor: Philogen S.p.A.

New P2 trial • Melanoma • Oncology • Solid Tumor

Intralesional administration of L19IL2/L19TNF in difficult-to-treat non-melanoma skin cancer shows a favorable safety profile and preliminary clinical activity (ESMO 2023) - P2 | "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. 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 • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • EDB-FN

Nidlegy Phase III PIVOTAL trial meets the study’s primary objective demonstrating statistically significant and clinically meaningful improvement in Recurrence-Free Survival for patients with locally advanced fully resectable melanoma (GlobeNewswire) - P3 | N=214 | PIVOTAL (NCT02938299) | "At median follow-up of 27.6 months in both groups, the study met its primary endpoint with a statistically significant and clinically meaningful improvement in RFS of the treatment arm compared to the control arm. This positive outcome was consistently in line with the Investigators’ Assessment: a significant reduction of the hazard risk ratio of 33% (HR = 0.67) and 37% (HR = 0.63), respectively, favoring the treatment arm, was observed both in the BICR and in the Investigators’ Assessment analysis....Treatment-related adverse events observed with Nidlegy™ were benign and manageable, consistent with the proposed mechanism of action and with the favorable safety profile previously reported in the Phase II study...The results, including sub-group analyses, will be presented at a forthcoming medical meeting."

P3 data • Melanoma • Oncology • Solid Tumor

DUNCAN: Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Feb 2023 ➔ Sep 2024 | Trial primary completion date: Nov 2022 ➔ Sep 2024

Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Genetic Disorders • Melanoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Skin Cancer

Intralesional administration of L19IL2/L19TNF in difficult-to-treat BCC patients shows favorable safety profile and leads to complete remission of tumor lesions (EADO 2023) - "Here, we investigated a combination of two antibody-cytokine fusion proteins Bifikafusp alfa and Onfekafusp alfa further referred as L19IL2 and L19TNF targeting the extradomain B of fibronectin (EDB) for the selective delivery of immunostimulatory payloads to the tumor site. Intralesional L19IL2/L19TNF administration demonstrates good safety profile and clinical efficacy in difficult to-treat BCC. Further investigation of intralesional L19IL2/L19TNF in BCC as well as in other NMSC indications is needed."

Clinical • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Philogen Announces Clinical Trial Collaboration with MSD (GlobeNewswire) - "Philogen...announces that it has entered into a Clinical Trial Collaboration and Supply Agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA). Under the terms of the supply agreement, MSD provides their anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), to be evaluated in combination with Philogen's immunocytokines L19IL2, L19TNF, and Nidlegy™ in a randomized Phase II clinical trial. The study provides an opportunity to explore the combination of immunocytokines and PD-1 blockade in stage III and IV unresectable melanoma patients who failed prior checkpoint inhibitor therapies."

Licensing / partnership • Basal Cell Carcinoma • Cutaneous T-cell Lymphoma • Kaposi Sarcoma • Melanoma • Merkel Cell Carcinoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Skin Cancer

KEYNOTE PRESENTATION: Antibody-Cytokine Fusions for the Treatment of Difficult-to-Cure Cancer Types: Emerging Clinical Results (PEGS 2023) - "In addition, results from clinical trials with Nidlegy in high-risk basal cell carcinoma patients, candidates for disfiguring surgery who experienced durable complete responses, will be shared. Other clinical trial results in “difficult-to-treat tumors” will be discussed."

Clinical • Basal Cell Carcinoma • Brain Cancer • CNS Tumor • Glioblastoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor

Sun Pharma and Philogen enter into an Exclusive Distribution, License, and Supply Agreement for Commercializing specialty product, NIDLEGY in Europe, Australia and New Zealand (GlobeNewswire) - "Sun Pharmaceutical Industries Limited...announced that they have entered into a licensing agreement for commercializing Philogen’s specialty product, Nidlegy™ (Daromun) in the territories of Europe, Australia and New Zealand. Nidlegy™, currently in Phase III clinical trials, is a new anti-cancer biopharmaceutical which is being developed by Philogen for the treatment of melanoma and non-melanoma skin cancers. Under the terms of the agreement, Sun Pharma will have exclusive rights to commercialise Nidlegy™ for indications of skin cancers in the territories of Europe, Australia and New Zealand."

Licensing / partnership • Melanoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Neo-DREAM: Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C 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

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