ZN-c3 + Niraparib for Ovarian Cancer

Not currently recruiting at 38 trial locations
PD
Overseen ByProject Director
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, ZN-c3 (Azenosertib) and niraparib (Zejula, a PARP inhibitor), for ovarian cancer unresponsive to platinum-based therapies. The trial aims to assess the safety and effectiveness of these treatments, either alone or combined, in controlling cancer growth. Individuals with recurring high-grade ovarian, primary peritoneal, or fallopian tube cancer, who have not found a cure with current treatments, might be suitable candidates. Participants should be able to take oral medication and have measurable recurring cancer. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires a minimum of 10 days without prior PARP inhibitors before starting the new treatment. Additionally, you cannot take medications with a known risk of Torsades de Pointes (a type of heart rhythm problem).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that ZN-c3, also known as azenosertib, is generally safe for people with platinum-resistant ovarian cancer. Research indicates that about 34.9% of patients respond to the treatment, and it is well-tolerated. These studies have reported no major safety concerns for ZN-c3.

For the combination of ZN-c3 and niraparib, research shows a similar response rate of around 35% in patients who have tried many other treatments. This suggests that the combination is also well-tolerated. The FDA has already approved niraparib for use in advanced ovarian cancer, confirming its safety in this context.

Overall, the available evidence suggests that both ZN-c3 alone and in combination with niraparib are safe for human use, with manageable side effects.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about ZN-c3 and Niraparib for ovarian cancer because these treatments offer a unique approach compared to existing options. Unlike traditional chemotherapy, which broadly targets fast-growing cells, ZN-c3 is designed to inhibit a specific enzyme called Wee1, potentially stopping cancer cells from repairing themselves. Niraparib, a PARP inhibitor, works by preventing cancer cells from repairing their DNA, leading to cell death. The combination of these treatments targets cancer cells in a more focused way, potentially increasing effectiveness and minimizing damage to healthy cells. This novel strategy could offer new hope for patients with ovarian cancer who have limited options.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that ZN-c3, which participants in this trial may receive as monotherapy, may help treat ovarian cancer unresponsive to platinum-based treatments, with about 34.9% of patients experiencing tumor shrinkage or halted growth. Another treatment arm in this trial uses ZN-c3 combined with niraparib, a drug already approved for some ovarian cancers. The response rate for this combination is similar, at about 35% in patients who have undergone many previous treatments. These early results suggest that ZN-c3, both alone and with niraparib, could effectively manage this challenging condition.12346

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with high-grade ovarian, peritoneal, or fallopian tube cancer that's resistant to platinum therapy. They must have relapsed within 6 months of treatment and be willing to provide tissue samples. Participants need measurable disease and good organ function but can't join if they have certain heart conditions, uncontrolled blood pressure, gastrointestinal issues affecting absorption, a history of MDS/AML or are on drugs with TdP risk.

Inclusion Criteria

Have demonstrated relapse within 6 months of platinum therapy (platinum-free interval <6 months)
Willingness to release archival tissue for research purposes or to undergo a tumor tissue biopsy prior to dosing on Cycle 1 Day 1
Must have measurable disease according to RECIST V1.1 criterion: defined as at least one lesion that can be accurately measured
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Exclusion Criteria

Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
Uncontrolled hypertension (Diastolic BP > 90 mmHg or Systolic BP > 140 mmHg)
A minimum of 10 days between termination of the prior PARPi and administration of ZN-c3 and niraparib treatment is required
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Phase 1/2 study to evaluate the safety, clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD) of ZN-c3 in combination with niraparib and ZN-c3 Monotherapy

30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Niraparib
  • ZN-c3
Trial Overview The study tests ZN-c3 alone and combined with niraparib in patients with platinum-resistant ovarian cancer. It aims to assess the safety and effectiveness of these treatments while also studying how the body processes them (pharmacokinetics) and their impact on the disease at a cellular level (pharmacodynamics).
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: ZN-c3 and NiraparibExperimental Treatment2 Interventions
Group II: ZN-c3Experimental Treatment1 Intervention

Niraparib is already approved in European Union, United States, Canada for the following indications:

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Approved in European Union as Zejula for:
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Approved in United States as Zejula for:
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Approved in Canada as Zejula for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

K-Group Beta

Lead Sponsor

Trials
6
Recruited
670+

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Lead Sponsor

Trials
8
Recruited
740+

Citations

Release DetailsIn these patients, an ORR of 34.8% (8/23; 95% CI: 16.4-57.3) and an mDOR of 5.2 months (95% CI: 2.8, 6.9) were observed. Full efficacy results ...
Azenosertib Shows Promising Efficacy in Platinum- ...Azenosertib monotherapy showed a 34.9% overall response rate in heavily pretreated, cyclin E1–positive, platinum-resistant ovarian cancer, with a median ...
Azenosertib Monotherapy Appears Safe and Effective in ...Azenosertib showed a 34.9% response rate in patients with cyclin E1–positive platinum-resistant ovarian cancer, with a median response duration ...
NCT05128825 | A Study of Azenosertib (ZN-c3) in Subjects ...This is a multi-part Phase 2 study to evaluate the efficacy and safety of azenosertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian ...
Correlation of cyclin E1 expression and clinical outcomes ...26.6% had a partial response (PR) and median progression free survival (PFS) = 9.03 mo (95%CI: 5.52-11.01). Azenosertib + PAC demonstrated the ...
Zentalis Pharmaceuticals Presents Updated Clinical Data ...Tumors overexpressing Cyclin E1 protein exhibit poorer outcomes after standard of care chemotherapy regimens," said Fiona Simpkins, M.D., ...
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