MP-VAC-209 is a Phase I/II, open label, single arm, multi-center study to assess safety, tolerability, and antitumor activity of vactosertib as a single agent in adolescents and adults with recurrent, refractory, or progressive osteosarcoma. Vactosertib is given orally, twice a day, to people 12 years of age and older who meet the criteria for study enrollment.
Subjects may be male or female, with adolescents aged 12 to 17 years and adults aged 18 years or older, as defined by applicable country-specific legal age classifications. No large studies have evaluated the use of vactosertib in younger pediatric subjects, for this reason, children younger than 12 years of age are excluded from this study.
Subjects must have clinical, radiologic, and histologic confirmation of Osteosarcoma (OSa), which must be documented.
Subjects must have measurable disease according to RECIST 1.1, diagnosed as recurrent, refractory or progressive osteosarcoma, and must have no available standard therapy.
Subjects must have recovered from the acute toxic effects with ≤ Grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 of all prior chemotherapy and immunotherapy with the exception of alopecia, anorexia, bone pain, and tumor pain prior to entering this study.
Subjects who have moderate or severe cardiovascular disease
Subjects who have uncontrolled intercurrent illness, including but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure (New York Heart Association Class III/IV), uncontrolled hypertension (≥150/90mmHg), unstable angina pectoris or myocardial infarction (≤ 6 months prior to screening), uncontrolled cardiac arrhythmia, clinically significant cardiac valvulopathy requiring treatment, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent
Subjects who have major abnormalities at the Investigator's discretion based on electrocardiogram (ECG)and Doppler ECHO and MUGA results at screening or within 14 days before screening. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms in both male and female calculated from 12-lead ECGs.
Subjects who have increase in brain natriuretic peptide (BNP) or increase in troponin (over 99th percentile upper reference limit) at Screening (based on the normal range of relevant study center)
Single group
Vactosertib
DrugVactosertib is given twice a day, five days on and two days off in four-week cycles. Vactosertib is a transforming growth factor-beta (TGF-β) type 1 receptor inhibitor.
Dose finding associated with the overall nature and severity of AEs associated with treatment.
For phase 1, Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) : incidence of DLT and adverse events, Changes from baseline in Physical Exam, Vital Signs, local laboratory and ECGs, For phase 2, Antitumor activity of Vactosertib and PK analysis : ORR, PFS, DCR, DOR, TTP, TTR and OS, PK parameters
Time to response(TTR)
To evaluate the time to response(TTR) from Vactosertib treatment to show PR or CR. To characterize the pharmacokinetics(PK) of Vactosertib to 6 patients assigned to dose- escalation phase and the firsts 12 patients assigned to the dose expansion phase.
Overall survival.
Overall survival (1 year) calculated from date of enrollment to the dates of documented evidence of progression or death up to 12 months.
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