ZN-c3
Azenosertib[THERAPEUTIC_PROFILE]
Cyclin E1-Positive PROC, Ovarian Cancer
A small molecule inhibitor
[3D_INTERACTIVE_CONFORMATION]
[CLINICAL_TRIALS_REGISTRY]
A Randomized, Open-Label Phase 3 Study of Azenosertib Versus Investigator's Choice of Chemotherapy in Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
Analysis Window: Up to approximately 24 months from the enrollment of the last subject
Analysis Window: Up to approximately 24 months and 30 days from the enrollment of the last subject
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
No descriptive logs found.
No descriptive logs found.
[DOSING_&_INTERVENTION_SPECIFICITIES]
The investigator will select the chemotherapy in accordance with the protocol defined requirements. The possible choices as defined by the protocol: * Paclitaxel * Gemcitabine * Pegylated liposomal doxorubicin (PLD) * Topotecan The selected chemotherapy will be administered intravenously
Azenosertib 400 mg will be administered orally.
A Phase 2 Open-Label, Multicenter Study To Evaluate Efficacy And Safety Of ZN-c3 In Subjects With High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer (DENALI / ZN-c3-005 / GOG-3066)
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to approximately 12 months from the enrollment of the last subject
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to approximately 12 months from the enrollment of the last subject
Analysis Window: Up to approximately 12 months from the enrollment of the last subject
Analysis Window: Up to approximately 12 months from the enrollment of the last subject
Analysis Window: Up to approximately 12 months from the enrollment of the last subject
Analysis Window: Up to approximately 12 months from the enrollment of the last subject
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule.
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule
Azenosertib 300mg administered once daily on a 5 days on, 2 days off intermittent schedule
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule
[DOSING_&_INTERVENTION_SPECIFICITIES]
Azenosertib (ZN-c3) will be administered orally.
A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Adult Women With Recurrent or Persistent Uterine Serous Carcinoma
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: 2 years
Analysis Window: 2 years
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: 2 years
Analysis Window: 2 years
Analysis Window: 2 years
Analysis Window: 2 years
Analysis Window: 2 years
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Azenosertib (ZN-c3) taken orally with food
[DOSING_&_INTERVENTION_SPECIFICITIES]
Azenosertib is an investigational drug.
A Biomarker Study of the Wee1 Inhibitor Azenosertib (ZN-c3) in Women With Recurrent or Persistent Uterine Serous Carcinoma
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 7 months
Analysis Window: At 6 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 7 months
Analysis Window: At 6 months
Analysis Window: Up to 7 months
Analysis Window: Up to 7 months
Analysis Window: 2 years
Analysis Window: Up to 7 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
25 participants will be enrolled and will complete study procedures as follows: * Baseline visit with assessments and CT or MRI scan. * CT or MRIs scans every 2 cycles. * Cycle 1 through End of Treatment: --Days 1 through 5, 8 through 12, and 15 through 19: Predetermined dose of Azenosertib 1x daily. * End of Treatment visit.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Wee1 inhibitor, 25mg and 100mg tablets, taken orally per protocol.
Phase 2 Single Arm Trial Testing the ZN-c3 WEE1 Inhibitor in Combination With Gemcitabine in Second-Line Advanced Pancreatic Adenocarcinoma
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: 18 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: 18 months
Analysis Window: 18 months
Analysis Window: 18 months
Analysis Window: 18 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Study procedures will be conducted as follows: * Cycle 1 - End of Treatment * Days 1 - 5 of 21-day cycle: Predetermined dose of ZN-c3 1x daily. * Days 8 - 12 of 21-day cycle: Predetermined dose of ZN-c3 1x daily. * Days 15 - 19 of 21-day cycle: Predetermined dose of ZN-c3 1x daily. * Day 1 and 8 of 21-day cycle: Predetermined dose of Gemcitabine 1x daily. * On-treatment tumor biopsy will be collected on either Cycle 1 Day 9 - 10 or Cycle 2 Day 9 - 10. * Tumor assessment by Computerized Tomography (CT) or Magnetic Resonance Imaging scan every 8 weeks while on treatment. * End of treatment visit with tumor assessment by CT or MRI and optional tumor biopsy. * Follow up visit every 2 months after treatment has ended.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Small molecule inhibitor of the WEE1 tyrosine kinase, tablet taken orally per protocol.
Nucleoside metabolic inhibitor, per standard care via intravenous infusion.
Phase I Study of ZN-c3 and Bevacizumab ± Pembrolizumab in Metastatic CCNE1 Amplified and TP53 Mutant Solid Tumors
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: through study completion, an average of 1 year
Analysis Window: through study completion, an average of 1 year
[SECONDARY_SUCCESS_ENDPOINTS]
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
ZN-c3 in combination with bevacizumab
ZN-c3 in combination with bevacizumab and pembrolizumab
[DOSING_&_INTERVENTION_SPECIFICITIES]
Given by PO 1 time a day with a glass (about 8 ounces) of water
Given by vein over about 30-60 minutes on Day 1 of each cycle
Given by vein over 30-60 minutes on Day 1 of each cycle.
A Phase 1 Study of ZN-c3 as a Single Agent in Subjects With Solid Tumors
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Through completion, average of 1 year
Analysis Window: Through completion, approx 6 months
Analysis Window: Through completion, approximately 6 months
Analysis Window: Through completion approximately 6 month
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Through completion
Analysis Window: Through completion
Analysis Window: Through completion.
Analysis Window: Through completion..
Analysis Window: Through completion...
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Subjects with solid tumors with advanced or metastatic disease who are refractory or ineligible to standard therapy(ies) or for whom no standard therapy is available.
Subjects with solid tumors with advanced or metastatic disease who are refractory or ineligible to standard therapy(ies) or for whom no standard therapy is available. This cohort will give subjects the option to continue treatment after PK assessments are completed.
Subjects with recurrent, platinum-resistant HGSOC; histologically confirmed USC; or either CCNE1-amplified/cyclinE1-positive solid tumors; or subjects who roll over from ZN-c3 pharmacology studies.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Azenosertib (ZN-c3) is a study drug
A Phase 1/2 Dose-Escalation and Dose-Expansion Study of ZN-c3 in Combination With Niraparib and ZN-c3 Monotherapy in Subjects With Platinum-Resistant Ovarian Cancer
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: 6 months
Analysis Window: 12 months
Analysis Window: 12 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: 30 months
Analysis Window: 30 months
Analysis Window: 30 months
Analysis Window: 30 months
Analysis Window: 30 months
Analysis Window: 30 months
Analysis Window: 30 months
Analysis Window: 30 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Azenosertib in combination with Niraparib
Azenosertib Monotherapy
[DOSING_&_INTERVENTION_SPECIFICITIES]
Azenosertib
Niraparib
A Phase 1b Study of ZN-c3 in Combination With Chemotherapy or Bevacizumab in Subjects With Ovarian, Peritoneal, or Fallopian Tube Cancer
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Through study completion, an average of 1 year
Analysis Window: Through Cycle 1 (cycle is 28 days for PLD or paclitaxel, and 21 days for carboplatin, or gemcitabine)
Analysis Window: Through study completion, an average of 1 year
Analysis Window: Through Cycle 1 (21 days)
[SECONDARY_SUCCESS_ENDPOINTS]
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Azenosertib in combination with carboplatin
Azenosertib in combination with pegylated liposomal doxorubicin (PLD)
Azenosertib in combination with paclitaxel
Azenosertib in combination with gemcitabine
Azenosertib in combination with bevacizumab
[DOSING_&_INTERVENTION_SPECIFICITIES]
Investigational drug
Carboplatin is an approved drug
Pegylated liposomal doxorubicin (PLD) is an approved drug
Paclitaxel is an approved drug
Gemcitabine is an approved drug
Bevacizumab is an approved drug
A Phase 1/2 Dose Escalation Study of the BCL-2 Inhibitor ZN-d5 and the WEE1 Inhibitor ZN-c3 in Subjects With Acute Myeloid Leukemia
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: At the end of Cycle 1 (each cycle is 28 days)
Analysis Window: Through study completion, typically < 12 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Through study completion, typically <12 months
Analysis Window: Through study completion, typically < 12 months
Analysis Window: Through study completion, typically < 12 months
Analysis Window: Through study completion, typically < 12 months
Analysis Window: Through study completion, typically < 12 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion
[DOSING_&_INTERVENTION_SPECIFICITIES]
Oral agent
Oral agent
A Phase I/II Single-arm Trial of Azenosertib (ZN-c3) Combined With Carboplatin and Pembrolizumab in Patients With Metastatic Triple-negative Breast Cancer (ZAP-IT)
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 3 weeks
Analysis Window: Up to 3 weeks
Analysis Window: Up to 6 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 48 months
Analysis Window: Up to 48 months
Analysis Window: Up to 5 years
Analysis Window: Up to 48 months
Analysis Window: Up to 48 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Participants will be enrolled in a standard 3+3 dose-escalation scheme to establish a Maximum Tolerated dose (MTD) of Azenosertib, starting at Dose Level 0, de-escalating to Dose Level -1, and escalating to Dose Levels 1 and 2. * Baseline visit with CT or MRI scan. * CT or MRI scan every 9 weeks until 27 weeks then every 12 weeks. * Cycle 1 through End of Treatment: * Days 1 through 5, 8 through 12, and 15 through 19 of 21 Day Cycle: Predetermined dose of Azenosertib 1 x daily. * Day 1 of 21 Day Cycle: Predetermined dose of Pembrolizumab 1x daily. * Days 1 and 8 of 21 Day Cycle: Predetermined dose of Carboplatin 1x daily. * End of Treatment visit * Follow up: every 6 months * Dose de-escalation and escalation will follow dose-limiting toxicities specifications (DLTs) per the protocol. The MTD is the highest dose level with ≤1 DLT in a cohort of 6 participants.
[DOSING_&_INTERVENTION_SPECIFICITIES]
WEE1 inhibitor, 25 or 100 mg tablet, taken orally per protocol.
Platinum coordination compound, 5-, 15-, 45-, and 60-mL vials, via intravenous (into the vein) infusion per institutional standards.
Humanized immunoglobulin G4 monoclonal antibody, 4-mL vials, via intravenous (into the vein) infusion per protocol.
A Phase 1/2, Open-Label, Multi-Center Study of ZN-c3 Administered in Combination With Encorafenib and Cetuximab in Adults With Metastatic Colorectal Cancer
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: From Lead-in Day -1 to Cycle 1 Day 28
Analysis Window: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: From first dose of any study intervention through 28 days after the last dose of any study intervention
Analysis Window: From first dose of any study intervention through 28 days after the last dose of any study intervention
Analysis Window: From first dose of any study intervention through 28 days after the last dose of any study intervention
Analysis Window: From first dose of any study intervention through 28 days after the last dose of any study intervention
Analysis Window: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Analysis Window: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Analysis Window: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Analysis Window: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
[DOSING_&_INTERVENTION_SPECIFICITIES]
ZN-c3 tablet by mouth, in combination with encorafenib
Encorafenib capsule by mouth, in combination with ZN-c3
Infusion
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
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Through Cycle 1 (21 days) Phase 1
Analysis Window: During phase 2, at 18 weeks
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: At 12 months
Analysis Window: At 12 months
Analysis Window: Through completion, approximately 42 months
Analysis Window: Through completion, approximately 42 months
Analysis Window: Through completion, approximately 42 months
Analysis Window: Through completion, approximately 42 months
Analysis Window: Through completion, approximately 42 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Azenosertib (ZN-c3) in combination with Gemcitabine
[DOSING_&_INTERVENTION_SPECIFICITIES]
Azenosertib is an investigational drug.
Gemcitabine is an approved drug