A Study of ZN-c3 in Patients With Platinum-Resistant Ovarian Cancer
- Provision of written informed consent prior to initiation of any study-related procedures that are not considered standard of care.
- Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
- ECOG performance status ≤ 2.
- Histologically or cytologically confirmed high-grade serous epithelial ovarian carcinoma, fallopian tube, or peritoneal carcinoma.
- Subjects must have received 1 or 2 prior chemotherapy regimens.
- The disease must be platinum-resistant, i.e., the Platinum-Free Interval (PFI) must have been < 6 months. Platinum refractory disease, i.e., PD during first-line platinum-based therapy is allowed.
- Measurable disease per RECIST version 1.1.
- Adequate hematologic and organ function as defined by the following criteria:
- ANC ≥ 1.5 × 10^9/L; excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim.
- Platelet count ≥ 100 × 10^9/L; excluding measurements obtained within 3 days after transfusion of platelets.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastases, AST and ALT ≤ 5 x ULN.
- Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min.
- Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) test and agree to use an effective method of contraception per institutional standard.
- Left ventricular ejection fraction (LVEF) ≥ 50% or within normal limits of the institution (only for subjects treated with PLD).
- Histology of abdominal adenocarcinoma of unknown origin or diagnosis of a borderline ovarian tumor.
- Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1:
- Major surgery within 28 days.
- Radiation therapy within 21 days.
- Autologous or allogeneic stem cell transplant within 3 months.
- A serious illness or medical condition(s) including, but not limited to, the following:
- Brain metastases that require immediate treatment or are clinically or radiologically unstable.
- Leptomeningeal disease that requires or is anticipated to require immediate treatment.
- Myocardial impairment of any cause.
- Significant gastrointestinal abnormalities.
- Active or uncontrolled infection.
- Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2 neuropathy, alopecia or skin pigmentation).
- Pregnant or lactating females (including the cessation of lactation) or females of childbearing potential who have a positive serum pregnancy test within 14 days prior to Cycle 1 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 > 450 msec, 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 long QT syndrome.
- Taking medications that lead to significant QT prolongation.
- Administration of strong and moderate CYP3A4 inhibitors and inducers as well as strong and moderate P-glycoprotein (P-gp) inhibitors.
This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability,
preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of ZN-c3. This
study consists of 2 cohorts in participants with platinum-resistant ovarian, peritoneal, or
fallopian tube cancer. One cohort will test a combination of ZN-c3 and pegylated liposomal
doxorubicin (PLD), and the other cohort will test a combination of ZN-c3 and carboplatin.
Trial Phase Phase I
Trial Type Treatment
- Primary ID ZN-c3-002
- Secondary IDs NCI-2020-07262
- Clinicaltrials.gov ID NCT04516447