This early phase I trial tests the safety and side effects of ZN-c3 in treating patients with triple-negative breast cancer or ovarian cancer that have spread to other parts of the body (metastatic or advanced). ZN-c3 is an enzyme inhibitor that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine the primary pharmacodynamic effect of wee1 inhibitor ZN-c3 (ZN-c3) in tumor biopsies from patients with advanced triple-negative breast cancer (TNBC) and ovarian cancer. II. To assess safety and tolerability of the proposed therapy. SECONDARY OBJECTIVES: I. To assess clinical benefit of TNBC and ovarian cancer patient from the proposed therapy. II. To determine time to disease progression. III. To assess participant survival on study. EXPLORATORY OBJECTIVES: I. To evaluate ZN-c3 pharmacokinetics (PK). II. To identify predictive biomarkers of sensitivity to therapy. III. To identify emerging mechanisms of resistance to therapy. OUTLINE: Patients receive Wee1 inhibitor ZN-c3 orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given PO
Percent decrease of phosphorylated CDK1 and/or Ki67, or p-HH3, or p-CHK1 in tumor cells
The point estimate of percentage decrease of either phosphorylated CDK1, or Ki67, or p-HH3, or p-CHK1, or combinations thereof in tumor cells (from baseline) after receiving ZN-c3 will be provided.
Time frame: Baseline to completion of on-treatment biopsy, up to 21 days
Incidence of adverse events
Incidence of grade \>= 3 toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Time frame: Day 1 to 30 days after last dose of study intervention
Clinical benefit rate (CBR)
CBR is the proportion of all participants that achieve a complete response (CR), partial response (PR) or stable disease (SD) \>= 6 months without evidence of radiologic progression to this point (i.e., CR + PR + SD)(per Response Evaluation Criteria in Solid Tumors \[RECIST\] v 1.1).
Time frame: Day 1 to end of treatment, approximately 12 months
CBR for ovarian cancer
CBR (i.e., CR + PR + SD) in the ovarian cancer cohort will also be assessed using the Gynecological Cancer Intergroup (GCIG) criteria.
Time frame: Day 1 to end of treatment, approximately 12 months
Time to disease progression
Measure of the length of time from date of study treatment start until the date of cancer progression.
Time frame: Day 1 to date of progression, assessed up to 1 year after discontinuing study drug
Progression free survival
Measure of the proportion of participants without disease progression starting from the time from cycle 1 day 1 dose administration to the time of documented disease progression or death from any cause.
Time frame: Day 1 to date of progression or death from any cause, assessed up to 1 year after discontinuing study drug
Overall survival
Measure of the proportion of participants that are alive starting from the time from cycle 1 day 1 dose administration to the time of death from any cause.
Time frame: Day 1 to death from any cause, assessed up to 1 year after discontinuing study drug
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