Fibromun (onfekafusp alfa) / Philogen - LARVOL DELTA

Multimodal management of melanoma treatment (EADO-WCM 2025) - "Results Subsequent staging examinations revealed further subcutaneous and bony metastases and treatment with dacarbazine (1000 mg/m², 11 cycles, 3 weekly) combined with radiotherapy (40Gy) was administered...Given the history of irHepatitis during nivolumab treatment, combined immunotherapy (pembrolizumab (200mg) and low-dose ipilimumab (1mg/kg) was introduced due to further disease progression...The metastases on the right lower leg were then treated with intralesional electrochemotherapy (bleomycin 30mg), with the aim of achieving loco-regional control...The potential benefit of re-challenge with immunotherapy has to be weighed against the risk of irAE recurrence on an individual basis. LAG3 inhibition, bispecific molecules (anti-PD-1 and LAG3) und antibody-cytokine fusions (L19IL2 and L19TNF) may represent treatment options in the second-line setting but require evaluation in clinical trials."

IO biomarker • Hepatology • Melanoma • Oncology • Retinal Disorders • Solid Tumor • BRAF • LAG3 • NRAS

Philogen completes patient enrollment of Phase III FIBROSARC trial in Soft Tissue Sarcoma (Indian Pharma Post) - "Sun Pharmaceutical Industries Limited and Philogen S.p.A. have announced the successful completion of patient enrollment in the Phase III FIBROSARC trial for Soft Tissue Sarcoma (STS). All ongoing Fibromun trials remain on track with their expected timelines...'We are also seeing faster-than-expected patient enrollment in the Glioblastoma trials. The Phase II GLIOSTAR trial, originally projected to complete enrollment by December 2025, is now expected to conclude recruitment in Q2 2025.'"

Enrollment closed • Enrollment status • Glioblastoma • Soft Tissue Sarcoma

FLASH: Efficacy and Safety of L19TNF in Previously Treated Patients with Advanced Stage or Metastatic Soft-tissue Sarcoma (clinicaltrials.gov) - P2 | N=98 | Active, not recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

GLIOSTELLA: A Study with L19TNF in Combination with Lomustine in Patients with Glioblastoma At Progression or Recurrence (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Philogen S.p.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Unbiased discovery of synergistic vulnerabilities against glioblastoma: An innovative in vivo CRISPR profiling platform to unleash the power of tumor-targeted cytokine therapy (SNO 2024) - "Our research marks a significant advancement in pursuing novel treatment strategies for glioblastoma. We have unveiled a range of synergistic combinations and paved the way for the rational design of combinatory treatment approaches to maximize the therapeutic efficacy of L19-TNF immunotherapy, laying the groundwork for future clinical translation."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Sun Pharma and Philogen enter into a global Exclusive Commercialization, License, and Supply Agreement for Commercializing the specialty product FIBROMUN (Sun Pharma) - "Sun Pharmaceutical Industries Limited...and Philogen S.p.A...announced that they have entered into a global licensing agreement for commercializing Philogen’s specialty product, Fibromun...Under the terms of the agreement, Sun Pharma will have the exclusive worldwide rights to commercialise Fibromun. Philogen will complete the ongoing pivotal clinical trials for the product, pursue Marketing Authorization with regulatory authorities, and manufacture commercial supplies. Sun Pharma will be responsible for commercialization activities."

Commercial • Glioblastoma • Soft Tissue Sarcoma

Unveiling synergistic strategies: CRISPR-guided optimization of L19-TNF immunocytokine therapy in glioblastoma (EANO 2024) - "Particularly combination therapies based on L19TNF, such as the combination with lomustine, have shown promising activity in preclinical models. Our research represents a significant step forward in the quest for innovative treatment strategies in glioblastoma. The CRISPR screening under immunotherapeutic selection has revealed a spectrum of synergistic partners and paved the way for a rational design of combinatory treatment approaches to maximize therapeutic efficacy, laying the groundwork for future clinical translation."

Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

FLASH: Efficacy and Safety of L19TNF in Previously Treated Patients With Advanced Stage or Metastatic Soft-tissue Sarcoma (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: Philogen S.p.A. | Trial primary completion date: Dec 2023 ➔ Dec 2024

Metastases • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

GLIOASTRA: Safety and Efficacy of Different Administration Sequences of L19TNF With Lomustine in Glioblastoma at First Progression (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Philogen S.p.A. | N=24 ➔ 0 | Not yet recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Trial withdrawal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

FIBROSARC: A Study Comparing the Efficacy of L19TNF+Doxorubicin vs Doxorubicin Alone as First-line Therapy in Patients With Advanced or Metastatic Soft Tissue Sarcoma (clinicaltrials.gov) - P3 | N=102 | Recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

DOXO75: Dose Finding Study of L19TNF and Doxorubicin in Patients With STS (clinicaltrials.gov) - P1 | N=2 | Active, not recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

GLIOSTAR: A Study to Evaluate Safety and Efficacy of L19TNF Plus Lomustine in Patients With Glioblastoma at First Progression (clinicaltrials.gov) - P1/2 | N=142 | Recruiting | Sponsor: Philogen S.p.A. | Trial primary completion date: Nov 2023 ➔ Mar 2025

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

GLIOSTELLA: A Study With L19TNF in Combination With Lomustine in Patients With Glioblastoma at Progression or Recurrence (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Philogen S.p.A.

Combination therapy • New P2 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Philogen provides update on pre-planned interim analysis of the Phase III FIBROSARC trial investigating Onfekafusp alfa (L19TNF) in patients with first-line advanced or metastatic Soft Tissue Sarcoma (GlobeNewswire) - P3 | N=102 | FIBROSARC (NCT04650984) | Sponsor: Philogen S.p.A. | "Philogen S.p.A...is pleased to announce that the Phase III FIBROSARC trial (NCT04650984) will continue as planned by the protocol. The decision was made by an Independent Data and Safety Monitoring Board (DSMB) following the review of efficacy and safety data in the pre-planned interim analysis....The 46 events required to trigger the interim analysis were reached on 9th November 2023, and at the time of this Press Release the study has enrolled 97 out of 118 patients across 24 clinical centers in Germany, Italy, France, Poland, and Spain. The enrolment of 118 patients is expected to be completed in 2024."

DSMB • Enrollment status • Soft Tissue Sarcoma

GLIOSTAR: A Study to Evaluate Safety and Efficacy of L19TNF Plus Lomustine in Patients With Glioblastoma at First Progression (clinicaltrials.gov) - P1/2 | N=142 | Recruiting | Sponsor: Philogen S.p.A.

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Phase I study results of the antibody-cytokine fusion protein L19TNF in combination with lomustine for patients with recurrent glioblastoma reveal promising safety and durable tumor responses (SNO 2023) - P1/2 | "Subsequent re-challenge with L19TNF and lomustine again led to a partial response. These encouraging results justify further investigations within the phase II part of the clinical trial that is recruiting patients in four countries."

Clinical • Combination therapy • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CRP • TNFA

CLINICAL OUTCOME AND TRANSLATIONAL INSIGHTS FROM A PHASE I/II TRIAL WITH THE TUMOR-TARGETING ANTIBODY-CYTOKINE FUSION PROTEIN L19TNF FOR PATIENTS WITH RECURRENT GLIOBLASTOMA (EANO 2023) - P1/2 | "CONCLUSIONThe intravenous administration of L19TNF is safe in patients with recurrent glioblastoma and shows pharmacodynamic effects at the tumor site. Ongoing studies investigate L19TNF in combination with temozolomide-based chemoradiation for patients with newly diagnosed glioblastoma (NCT04443010) and in combination with lomustine for patients at first progression (NCT04573192)."

Clinical • Clinical data • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

DOXO75: Dose Finding Study of L19TNF and Doxorubicin in Patients With STS (clinicaltrials.gov) - P1 | N=2 | Active, not recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

GLIOMOON: Safety and Efficacy of L19TNF in Patients With Isocitrate Dehydrogenase (IDH) Wildtype WHO Grade III / IV Glioma at First Relapse (clinicaltrials.gov) - P1/2 | N=20 | Completed | Sponsor: Philogen S.p.A. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

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

Targeted delivery of tumor necrosis factor in combination with CCNU induces a T cell-dependent regression of glioblastoma. (PubMed, Sci Transl Med) - P1/2 | "On the basis of these encouraging results, we translated this treatment combination to patients with glioblastoma. The clinical translation is ongoing but already shows objective responses in three of five patients in the first recurrent glioblastoma patient cohort treated with L19TNF in combination with CCNU (NCT04573192)."

Combination therapy • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • TNFA

Philogen Publishes New Data on a Fibromun-based treatment combination in Science Translational Medicine in collaboration with the University Hospital Zürich (GlobeNewswire) - "Philogen...announces the publication of the latest results of Fibromun (L19TNF, Onfekafusp alfa) in combination with lomustine (an alkylating agent) for the treatment of glioblastoma in Science Translational Medicine describing how the combination treatment cured orthotopic glioma-bearing mice and mediated durable objective responses and major tumor shrinkage in patients with recurrent glioblastoma....'We are excited to release this follow-up work based on the Science Translational Medicine paper published together with Philogen back in 2020. The preclinical anti-tumor activity of the combination of Fibromun with lomustine chemotherapy is very promising and the emerging clinical results of the ongoing Phase I/II trial NCT04573192 provide hope for better therapeutic opportunities for patients affected by this serious disease. We now look forward to exploring this promising approach in the Phase II randomized part which is currently starting.'"

Preclinical • Trial status • Glioblastoma • Oncology • Solid Tumor

Decreasing toxicity of immunocytokines by transient and selective inhibition of their intracellular signaling activation (AACR 2023) - "L19-TNF and L19-IL12 are two clinical-stage antibody-cytokine fusion proteins that display potent activity by triggering the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and Janus Kinase 2 (JAK2) signaling pathways, respectively (Amin et al. Our data demonstrate that the pre-treatment with Ruxolitinib restricted the pro-inflammatory effects of L19-murIL12 to the tumor site, protecting the mice from body weight loss as well as reducing blood cytokine levels and hepatotoxicity. Overall, this preclinical work is of clinical relevance, as patients treated with targeted cytokines could potentially benefit from judicious combinations treatments using small molecule inhibitors."

Oncology • CDK7 • IL12A • RIPK1

The combination of lomustine and the immunocytokine L19TNF is a promising treatment for recurrent glioblastoma (SNO 2022) - P1/2 | "Treatment options for recurrent glioblastoma after standard of care chemoradiation are limited Several immunotherapeutic strategies including peptide vaccination and immune checkpoint inhibition have so far failed to improve survival and except from potentially regorafenib, no other agent has demonstrated superior activity to lomustine. Investigations of the mechanism of action revealed that lomustine plus L19TNF led to intratumoral necrosis, DNA damage and triggered a strong local anti-tumor immune response with increased MHC-I expression, presentation of neoepitopes and increased abundance of tumor-infiltrating lymphoid cells. In the first patients treated within a phase I/II clinical trial (NCT04573192), the treatment was well tolerated, and durable objective tumor responses and disease stabilizations could be observed also in patients with an unmethylated MGMT promoter."

IO biomarker • Brain Cancer • Glioblastoma • Immune Modulation • Inflammation • Oncology • Solid Tumor

PHASE II STUDY OF THE ANTIBODY-CYTOKINE FUSION PROTEIN L19TNF PLUS DACARBAZINE FOR PRETREATED PATIENTS WITH ADVANCED OR METASTATIC SOFT TISSUE SARCOMA: RESULTS OF THE RUN-IN PART (CTOS 2021) - P2 | "L19TNF can be safely applied in combination with dacarbazine and induces tumor responses in patients with previously pretreated advanced or metastatic soft tissue sarcomas."

Clinical • P2 data • Anemia • Hematological Disorders • Hypotension • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TNFA