Abstract 1553TiP
Background
Recombinant human tumor necrosis factor (TNF) is a potent proinflammatory and cytotoxic cytokine that is approved in the EU for the therapy of soft tissue sarcoma (STS) of the limbs, used in combination with melphalan in an isolated-limb perfusion procedure. Although TNF is one of the most potent antitumor cytokines, the considerable therapeutic potential of natural TNF cannot be fully exploited due to severe side effects, which preclude achievement of therapeutically active concentrations in the tumor. To circumvent these issues, the fully human antibody-cytokine fusion protein L19TNF, composed of the vascular targeting antibody fragment scFv(L19) fused to human recombinant TNF, has been designed to selectively deliver TNF to the tumor tissue while sparing normal organs. L19TNF has demonstrated substantial therapeutic activity in preclinical models of sarcoma when administered alone or in combination with doxorubicin, leading to hemorrhagic tumor necrosis and immune-mediated tumor rejection. A phase Ib dose escalation study has determined the recommended dose of L19TNF as 13 μg/kg, when administered systemically in combination with doxorubicin.
Trial design
This phase III, multi-center, open-label, randomized trial plans to enroll 118 patients. L19TNF (13 μg/kg, days 1, 3, and 5, q3w) will be investigated in combination with doxorubicin (60 mg/m2, day 1) versus doxorubicin alone (75 mg/m2) in patients with unresectable or metastatic STS as first-line therapy. The primary endpoint is progression-free survival (PFS). Secondary Endpoints include overall-survival (OS) and overall response rate (ORR). The study is powered to detect an improvement of median PFS from 4.4 months to 8.0 months in combination-treated patients, with a sample size of 118. Eligibility criteria include high-grade advanced or metastatic STS, measurable disease according to RECIST 1.1, age 18 - 75 years, no prior therapy (except surgery and/or radiation) for the metastatic stage of STS, ECOG performance status of ≤ 2, and adequate organ function.
Clinical trial identification
NCT04650984.
Editorial acknowledgement
Legal entity responsible for the study
Philogen S.p.A.
Funding
Philogen S.p.A.
Disclosure
C. Schliemann: Financial Interests, Institutional, Advisory Board: AbbVie; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche. D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint; Financial Interests, Institutional, Invited Speaker: PharmaMar; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: EUSA-Pharma; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Other, Scientific lead of a trial with funding from Novartis: Novartis; Financial Interests, Institutional, Principal Investigator: PharmaMar; Financial Interests, Institutional, Principal Investigator: Roche. A. Flörcken: Financial Interests, Personal, Other, Travel/Accommodation/Expenses: PharmaMar; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Ipsen. M. Ahrens: Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: PharmaMar. E. Palmerini: Financial Interests, Institutional, Advisory Board: Deciphera; Financial Interests, Institutional, Advisory Board: Eusa Pharma; Financial Interests, Institutional, Advisory Board: SynOx Therapeutics. S. Stacchiotti: Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Amgen ; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK. G. Grignani: Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: EISAI; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: GSK. P. Rutkowski: Financial Interests, Personal, Advisory Board: Blueprint Medicines; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Personal, Officer: ASCO; Non-Financial Interests, Personal, Member of the Board of Directors: Polish Society of Surgical Oncology. R. Ullrich: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: Böhringer Ingelheim; Financial Interests, Institutional, Advisory Board: Novartis. T. Hemmerle: Financial Interests, Personal, Full or part-time Employment: Philogen S.p.A.. D. Neri: Financial Interests, Personal, Full or part-time Employment: Philogen; Financial Interests, Personal and Institutional, Stocks/Shares: Philogen. T. Kessler: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Invited Speaker: Pharmamar. All other authors have declared no conflicts of interest.