On February 20, 2024 Philogen S.p.A. (BIT:PHIL) reported that the Phase III FIBROSARC trial (NCT04650984) will continue as planned by the protocol (Press release, Philogen, FEB 20, 2024, View Source [SID1234640287]). 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.

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FIBROSARC is a Phase III 1:1 randomized trial (NCT04650984) which studies L19TNF in combination with doxorubicin (Experimental Arm) versus doxorubicin alone (Control Arm) in 118 patients as first-line therapy for advanced or metastatic Soft Tissue Sarcoma (STS). The primary objective of the study is Progression Free Survival (PFS), with an estimated 45% reduction in the risk of progression in the Experimental Arm (Hazard Ratio 0.55). The pre-planned interim analysis was carried out at 50% of the expected events (i.e., one event corresponds to a disease progression or death) necessary for the primary outcome.

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.

Prof. Dario Neri, co-founder, CEO and CSO of Philogen, commented: "We are very pleased with the recommendation of the DSMB to continue the study as planned by the protocol. The Phase III FIBROSARC trial was designed to demonstrate a significant clinical benefit of L19TNF plus doxorubicin compared to doxorubicin alone. If the final analysis is successful, the study is expected to provide an innovative treatment option for patients with advanced or metastatic STS, for whom no new paradigm-shifting therapies have been available in the last decades."

Alfredo Covelli, MD, Chief Medical Officer of Philogen, commented: "Advanced or metastatic STS are aggressive tumors still treated with chemotherapy-based regimens that were approved in the 1970s. Most innovative therapies, such as immune checkpoint inhibitors, failed to provide a significant benefit to this patient population. We are excited to record the outcome of the interim analysis of FIBROSARC and look forward to seeing the final analysis."

L19TNF is also being evaluated in (i) a Phase IIb randomized trial in first-line metastatic Leiomyosarcoma in the United States (NCT03420014), (ii) a Phase II randomized trial in pre-treated advanced or metastatic Soft Tissue Sarcoma in Europe (NCT04733183), (iii) a Phase II randomized trial in Glioblastoma at first progression in Europe (NCT04573192), and (iv) a Phase I/II/IIb trial in newly diagnosed Glioblastoma in Europe (NCT04443010). Philogen is currently launching a new Phase II study in Glioblastoma at first or later progression in the United States, based on the very encouraging preliminary data observed in the European study. These results have already been published in the journal Science Translational Medicine in 2023 (Look at al. Sci. Trans. Med. 2023, 15:eadf2281).

About Onfekafusp alfa (L19TNF, also known as Fibromun)

L19TNF is a biopharmaceutical product, proprietary to Philogen, studied for the treatment of advanced Soft Tissue Sarcoma and Glioblastoma. It consists of the L19 antibody genetically fused to Tumor Necrosis Factor (TNF). L19 binds selectively to the Extra Domain B of Fibronectin, a protein expressed in tumors (and other diseases) but absent in most healthy adult tissues. TNF is a pro-inflammatory cytokine with anti-tumor activity that is preferentially localized by the L19 antibody to neoplastic masses. L19TNF is administered via a two-hour intravenous infusion. Late-stage clinical trials with registration potential are on-going in Soft Tissue Sarcoma and Glioblastoma. The product has pan-tumoral potential and could be explored for the therapy of other cancer types (e.g., lung, breast, colon, prostate cancers).

About FIBROSARC Phase III study (NCT04650984)

FIBROSARC is a Phase III international, multi-center, randomized, comparator-controlled, parallel-group study in subjects with advanced or metastatic soft tissue sarcoma. In the study, 118 patients will be enrolled and parallel assigned in a 1:1 fashion to one of two different arms, as follows:

Experimental Arm: Patients will receive 13 μg/kg L19TNF on days 1, 3 and 5 every 3 weeks in combination with 60 mg/m2 doxorubicin (once every 3 weeks).

Control Arm: Patients will receive 75 mg/m2 doxorubicin once every 3 weeks. The sample size is calculated based on a 2-sided significance level of 5% and an 80% power, assuming a 15% rate for permanent early censoring. The statistical analysis is designed to discriminate 8 months median PFS (mPFS) in the Experimental Arm versus 4.4 months mPFS in the Control Arm. The primary analysis of PFS will occur after approximately 92 PFS events.

About advanced or metastatic Soft Tissue Sarcoma

STS is a rare group of mesenchymal cancers originating from connective tissues, which collectively account for 1% of all adult cancers. Surgery is the first line of treatment for early stage and localized disease. However, distant metastases occur in many patients, especially in those with high-grade tumors. For patients with unresectable STS, chemotherapy is the standard of treatment and doxorubicin is the recognized standard of care for first line advanced or metastatic STS.