Abstract 1554TiP
Background
Although tumor necrosis factor (TNF) is one of the most potent antitumor cytokines, its unacceptable toxicities do not allow for systemic administration of therapeutically active doses. L19TNF is a fully human antibody-cytokine fusion protein, composed of the neovascular targeting antibody fragment scFv(L19) fused to human recombinant TNF, that selectively delivers therapeutically relevant doses of TNF to the tumor tissue while sparing normal tissues. L19TNF has demonstrated substantial therapeutic activity in preclinical models of sarcoma when administered alone or in combination with chemotherapy, leading to hemorrhagic tumor necrosis and immune-mediated tumor rejection. The dose of 13 μg/kg L19TNF, when administered systemically has previously been established as recommended dose as monotherapy and in combination with chemotherapy.
Trial design
This is a phase II, multi-center, open-label, randomized trial of L19TNF (13 μg/kg, days 1, 3, and 5, q3w) in combination with dacarbazine (day 1) versus dacarbazine alone (1000 mg/m2) in patients with unresectable or metastatic STS, who received at least two prior systemic therapies. The dose of dacarbazine in combination with L19TNF is explored in a run-in part of the study with up to 12 patients. The primary endpoint is progression-free survival (PFS). The study is powered to detect an improvement of median PFS from 2.6 months to 5.2 months in combination-treated patients, with a sample size of 86 patients in the randomized part of the study. Eligibility criteria include grade 2-3 advanced or metastatic soft tissue sarcoma, measurable disease according to RECIST 1.1, age 18 - 80 years, ECOG performance status of ≤ 2, and adequate organ function.
Clinical trial identification
NCT04733183.
Editorial acknowledgement
Legal entity responsible for the study
Philogen S.p.A.
Funding
Philogen S.p.A.
Disclosure
T. Kessler: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Invited Speaker: PharmaMar. 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: Lily; 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. P. Reichardt: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: Blueprint; Financial Interests, Institutional, Advisory Board: Clinigen; Financial Interests, Institutional, Advisory Board: Deciphera; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Mundibiopharma; Financial Interests, Institutional, Invited Speaker: PharmaMar; Financial Interests, Institutional, Advisory Board: PharmaMar; Financial Interests, Institutional, Advisory Board: Roche. 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: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bayer. G. Grignani: Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: EISAI; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Glaxo. 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. 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 S.p.A.; Financial Interests, Personal, Stocks/Shares: Philogen S.p.A.. 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.