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

Efficacy and safety of doxorubicin combined with the tumor-targeting antibody-cytokine fusion protein L19TNF as first-line therapy in advanced or metastatic soft tissue sarcoma: results from the phase III FIBROSARC trial (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

L19TNF in combination with lomustine chemotherapy for patients with recurrent glioblastoma: A randomized multicenter Phase II study (EANO 2026) - P1/2 | "This is the first randomized multicenter study with an intravenously administered tumor-targeted cytokine for patients with glioblastoma. The intravenous administration of L19TNF in combination with lomustine was safe and well-tolerated, but the study did not meet its primary endpoint. Translational investigations using imaging data, blood samples and tissue samples are ongoing."

Clinical • Combination therapy • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • TNFA

Efficacy and safety of the immunocytokine L19TNF in combination with lomustine as treatment for recurrent glioblastoma: Results of the GLIOSTELLA phase 2 trial (SNO 2026) - No abstract available

Clinical • Combination therapy • P2 data • Brain Cancer • Glioblastoma • Solid Tumor

Turning cold tumors hot: Targeted TNF potentiates the activity of bispecific T cell engagers in solid tumors (AACR 2026) - "Here, we introduce a novel dual-modality approach combining the TNF-based fusion protein directed to the extradomain B (EDB) of fibronectin, L19-TNF, which induces localized intratumoral inflammation and facilitates T cell infiltration, with a CD3-based bispecific T cell engager (TCE) targeting CEA, which mediates antigen-specific cytotoxicity...Furthermore, mechanistic analyses revealed enhanced TCE extravasation, upregulated ICAM-1 expression, and increased CD8⁺ T-cell infiltration, indicating vascular modulation and remodeling of the TME toward an inflamed, "hot" phenotype. These findings confirm that targeted delivery of TNF to the TME can effectively enhance the activity of immunotherapeutic agents, such as T cell redirecting therapies, in challenging tumor settings."

Bispecific • IO biomarker • Late-breaking abstract • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CEACAM5 • ICAM1

Targeted TNF Potentiates the Activity of Bispecific T-cell Engagers in Solid Tumors by Turning Cold Tumors Hot. (PubMed, Cancer Immunol Res) - "In this study, we report a dual-modality approach to treating colorectal cancer by combining the tumor necrosis factor (TNF)-based fusion protein directed to the extradomain B (EDB) of fibronectin, L19-TNF, which induces localized intratumoral inflammation and facilitates T-cell infiltration, with a CD3-based bispecific T-cell engager (TCE) targeting carcinoembryonic antigen (CEA), which mediates antigen-specific cytotoxicity...Furthermore, mechanistic analyses revealed enhanced TCE extravasation, upregulated intercellular adhesion molecule 1 expression, and increased CD8+ T-cell infiltration, indicating vascular modulation and remodeling of the TME toward an inflamed "hot" phenotype. These findings confirm that targeted delivery of TNF to the TME can effectively enhance the activity of immunotherapeutic agents, such as T cell-redirecting therapies, in challenging tumor settings."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CEACAM5 • ICAM1 • TNFA

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

Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Sun Pharma’s Cancer candidate Fibromun fails to meet primary endpoints in mid-stage studies (The Economic Times) - "In an intimation to the stock exchange, the company disclosed, under the Phase II FLASH study, the drug failed to establish its efficacy in ensuring 'Progression Free Survival' (PFS) among patients with soft tissue sarcoma...Furthermore, against the second targeted indication: glioblastoma, the Phase II GLIOSTAR trial conducted in 163 second-line patients did not meet its primary endpoint of overall survival."

P2 data • Glioblastoma • Soft Tissue Sarcoma

...Philogen —which is handling the clinical and regulatory responsibilities— has decided to initiate a new Phase III registrational study: FIBROSARC-2 to evaluate its overall survival (OS) and a request for Parallel Scientific Advice with the US FDA and EMA has been submitted to define the design of the trial. (The Economic Times) - "The design of these studies has already been discussed with the relevant regulatory authorities, and the enrolment of the first patients is expected in the second quarter of 2026."

New P3 trial • Liposarcoma • Sarcoma

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