A Phase I/II, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib as a Single Agent in Adolescents and Adults With Recurrent, Refractory or Progressive Osteosarcoma

This is a Phase I/II, open label, single arm, proof of concept, multi-center (global) study to assess safety, tolerability, pharmacokinetics and antitumor activity of vactosertib as a Single Agent in Adolescents and Adults with Recurrent, Refractory or Progressive Osteosarcoma or bone lesions that have progressed, relapsed or are refractory to standard systemic therapy. Adolescents are defined as subjects aged 12 to <18-year-old.

During the Phase I part of the trial, dose limiting toxicity will be used to decide dose escalation according to the standard 3+3 rules to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) in adults and adolescents.

Dose escalation will be conducted sequentially and independently in adults and adolescents, respectively. Dose escalation in adolescents will not start before dose escalation in adults is completed. Data from the Phase I part of the trail in adults will be reviewed by the DSMB before opening the Phase II part. Data from the Phase I in adolescents will be reviewed by the DSMB before each dose (de-)escalation. As soon as the RP2D in adolescents is established, adolescents will be enrolled in Phase II.

During Phase II, subjects will be enrolled at the RP2D determined independently for adults and adolescents. Data of the subjects enrolled in the Phase II will be pooled with data of subjects enrolled at the same dose level during Phase I to evaluate the efficacy in a total of 42 adult and adolescent subjects.

In all parts of the study, the DSMB will convene upon occurrence of a grade 5 or any two sequentially occurring grade 4 drug related adverse events. In such case, accrual may not resume unless the DSMB has conducted a review and offered a recommendation to continue the study.