A Study of Azenosertib (ZN-c3) in Combination With Gemcitabine in Subjects With Osteosarcoma

A Phase 1/2 Dose Escalation and Dose Expansion Study of ZN-c3 in Combination With Gemcitabine in Adult and Pediatric Subjects With Relapsed or Refractory Osteosarcoma

This is a phase 1/2 study of azenosertib (ZN-c3) in combination with gemcitabine in adult and pediatric subjects with relapsed or refractory osteosarcoma.

This is a phase 1/2 dose escalation and dose expansion study, evaluating the clinical activity and safety, pharmacodynamics, and pharmacokinetics of azenosertib (ZN-c3) in combination with gemcitabine in relapsed or refractory osteosarcoma.

Inclusion Criteria:

• Age ≥ 12 years at the time of informed consent
• Bodyweight ≥ 40 kg
• Histologically documented relapsed or metastatic osteosarcoma.
• Must have measurable disease according to RECIST Guideline version 1.1 criteria.
• Adequate hematologic and organ function.
• Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception per institutional standard prior to the first dose and for 6 months after study treatment discontinuation.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

• Unresolved toxicity of Grade >1 attributed to prior therapies (excluding: Grade ≤2 neuropathy, alopecia, or skin pigmentation)
• Prior therapy with a WEE1 inhibitor
• A serious illness or medical condition(s).
• Pregnant or lactating females. Females of childbearing potential with a positive serum pregnancy test <14 days to Day 1.
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
• 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >470 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid.
• History or current evidence of congenital or family history of long QT syndrome or Torsades de Pointes (TdP).
• Taking medications with a known risk of TdP.
• Administration of strong and moderate CYP3A4 inhibitors/inducers and strong and moderate P-gp inhibitors.