Fibromun (onfekafusp alfa) / Philogen, Sun Pharma - LARVOL DELTA

Sun Pharma’s partner Philogen reports positive survival trends in Fibromun Phase III study for soft tissue sarcoma (Business Upturn) - "Key findings from the FIBROSARC study: At the time of the final analysis involving 131 randomized patients and 92 PFS events: Median PFS (mPFS) was 7.9 months for the combination arm versus 4.6 months for doxorubicin alone. Objective Response Rate (ORR) stood at 19% with Fibromun plus doxorubicin compared to 14.3% with doxorubicin alone. Median Overall Survival (mOS) reached 28.3 months versus 19.6 months for the control group, though the OS data remain immature with 54 events recorded so far."

P3 data • Soft Tissue Sarcoma

L19TNF in combination with temozolomide-based chemoradiation for patients with newly diagnosed glioblastoma shows promising safety and overall survival signals in a Phase I study (EANO 2025) - P1/2 | "The intravenous administration of L19TNF is safe in patients with newly diagnosed glioblastoma and shows promising activity. These encouraging results warrant further investigations within the Phase II part of the clinical trial."

Clinical • Combination therapy • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EDB-FN

In vivo CRISPR screening uncovers vulnerabilities for cancer immunotherapy against glioblastoma (EANO 2025) - "L19-TNF, a tumor-targeted cytokine-based therapy that triggers anti-tumor immunity, is currently being tested in clinical trials for newly diagnosed and recurrent glioblastoma patients... Our research marks a considerable advancement in systematically uncovering gene candidates using in vivo CRISPR screening. These findings lay the foundation for the rational design of synergistic approaches, offering exciting prospects for more effective combination therapies for glioblastoma."

IO biomarker • Preclinical • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

IMAGLIO: A Study to Evaluate the Safety and Efficacy of L19TNF With Alkylating Chemotherapy for Patients With Recurrent IDH-mutant Astrocytoma or Oligodendroglioma (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P2 trial • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor

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