Dose Finding Study of L19TNF and Doxorubicin in Patients With STS

Summary

Participation Requirements

Description

Open-label, phase 1 dose confirmation study in patients with advanced, unresectable and/or metastatic soft tissue sarcoma. Six (6) Patients will be enrolled sequentially and will be treated according to the following scheme: • Doxorubicin 75 mg/m2 i.v. on day 1 of each 21-day cycle L19TNF 13 µg/kg i...

Open-label, phase 1 dose confirmation study in patients with advanced, unresectable and/or metastatic soft tissue sarcoma. Six (6) Patients will be enrolled sequentially and will be treated according to the following scheme: • Doxorubicin 75 mg/m2 i.v. on day 1 of each 21-day cycle L19TNF 13 µg/kg i.v. on day 1,3 and 5 of each 21-day cycle Initiation of the study treatment for an individual subject will occur no less than 3 days after initiation of the study treatment for the previous patient. Not more than 2 patients are to be treated simultaneously in Cycle 1. Should unacceptable toxicities occur in ? 2 patients during the observation period from Day 1 to Day 21 (first cycle), enrollment will be stopped. If a patient is not evaluable for unacceptable toxicity, he/she will be replaced. Patients will be treated in repeated cycles until the treatment or when one of the following criteria are met: Unacceptable toxicity Disease Progression or relapse The patient or the investigator requests the treatment discontinuation The patient meets a withdrawal criterion. Patients with SD or PR (according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 evaluation) after the maximum of 6 cycles of study treatment, will receive maintenance therapy for up to 18 maintenance cycles from start of treatment, toxicity or until disease progression occurs. Maintenance can start immediately after the end of cycle 6 and consists infusions of L19TNF on Day 1 of each maintenance cycle (every 3 weeks) and doxorubicin on Day 1 of maintenance cycle 1 and 2 (if appropriate). The primary objective is to evaluate the safety of L19TNF in combination with doxorubicin and to establish a recommended dose (RD), assessed as follows: Adverse events (AEs), serious adverse events (SAE) and drug induced liver injury (DILI) assessment based on Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 Standard laboratory (hematology, biochemistry and urinalysis) parameters. Electrocardiogram (ECG) and echocardiogram (ECHO) findings. In particular, data about QT/QTc intervals will be collected and analyzed for QT/QTc prolongation potentially caused by treatment. Physical examination findings including assessment of vital signs and physical measurements. The secondary objective of the study is to evaluate signs of efficacy measured as progression-free survival (PFS) rate at 3, 6, 9, 12 and 18 months. The other secondary objectives of the study are as follows: Efficacy of L19TNF in combination with doxorubicin: Overall response rate (ORR, consisting of CR and PR). Disease Control Rate (DCR, i.e. complete response (CR), partial response (PR) and stable disease (SD)) Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF. Characterization of pharmacokinetics (PK) of L19TNF and doxorubicin

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