ZN-c3 for Ovarian Cancer

Recruiting at 14 trial locations

Overseen By K-Group, Beta, Inc., a subsidiary of Zentalis Pharmaceuticals

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: K-Group Beta

Disqualifiers: Brain metastases, Myocardial impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 28

Duration: 40 months

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ZN-c3 (also known as Azenosertib) for ovarian cancer. Researchers aim to assess its safety and effectiveness when combined with other cancer drugs. The trial includes different groups, each receiving ZN-c3 with a different partner drug, such as bevacizumab or paclitaxel. It seeks participants with high-grade ovarian cancer who have already tried one or two other treatments. This trial may suit those with advanced or metastatic ovarian, fallopian tube, or peritoneal cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that azenosertib (ZN-c3) has been tested for safety in people with platinum-resistant ovarian cancer. In these studies, about 34.9% of patients, who had already received many treatments, responded to azenosertib. While promising, some safety concerns exist. The FDA has placed a partial hold on certain azenosertib studies, indicating a need for further investigation to address these issues.

The treatment has been tested in combination with other drugs such as bevacizumab, paclitaxel, PLD (pegylated liposomal doxorubicin), gemcitabine, and carboplatin. Each combination may cause different side effects, but specific details on these side effects are not available in current sources.

As this is a Phase 1 trial, the primary goal is to ensure the treatment's safety and understand the body's reaction to it. Although earlier studies provide some safety information, discussing expectations and the suitability of joining the trial with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ZN-c3 for ovarian cancer because it introduces a new approach by targeting a key enzyme involved in cancer cell survival, known as WEE1. Unlike existing treatments such as carboplatin or paclitaxel, which work by damaging DNA or disrupting cell division, ZN-c3 aims to inhibit this enzyme, potentially leading to more effective cancer cell death with fewer side effects. Additionally, ZN-c3 is being tested in combination with other drugs like bevacizumab and paclitaxel, which could enhance its effectiveness, offering a promising new strategy in ovarian cancer treatment.

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

Research has shown that ZN-c3, also known as azenosertib, could effectively treat ovarian cancer. In earlier studies, about 34.9% of patients with a specific type of ovarian cancer unresponsive to standard treatments saw their tumors shrink when treated with azenosertib alone. This means roughly one in three patients experienced tumor reduction, with effects lasting an average of about 5.2 months. The drug targets a protein that aids cancer cell growth, offering a new way to potentially slow or stop tumor growth. In this trial, azenosertib will be combined with other treatments such as bevacizumab, paclitaxel, PLD, gemcitabine, or carboplatin to evaluate its effectiveness in various combinations. ^{1 2 3 4 6}

Who Is on the Research Team?

Philippe Pultar, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for women over 18 with high-grade serous ovarian, fallopian tube, or peritoneal carcinoma that's resistant to platinum-based therapy. They must have had 1-2 prior treatments and measurable disease. Participants need proper organ function, a negative pregnancy test, and agree to use contraception.

Inclusion Criteria

I am a woman over 18 or the legal adult age in my country.

My blood and organs are functioning well.

I can take care of myself and do some daily activities.

Exclusion Criteria

I am not pregnant, breastfeeding, or have a positive pregnancy test.

I do not have another cancer that is spreading or needs treatment.

Your ECG shows a specific measurement called corrected QT interval (QTcF) that is longer than 480 milliseconds, unless you have certain heart conditions that affect this measurement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZN-c3 in combination with chemotherapy or bevacizumab to evaluate safety, tolerability, and clinical activity

40 months

Multiple visits per cycle, each cycle is 28 days for PLD or paclitaxel, and 21 days for carboplatin, gemcitabine, or bevacizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ZN-c3

Trial Overview The study tests ZN-c3 in combination with other cancer drugs (Carboplatin, Pegylated liposomal doxorubicin, Paclitaxel, Gemcitabine) on patients with platinum-resistant ovarian cancer. It aims to assess safety, tolerability and preliminary effectiveness of the drug mix.

How Is the Trial Designed?

Group I: Combination with paclitaxel Experimental Treatment 2 Interventions

combined with azenosertib

Group II: Combination with gemcitabine Experimental Treatment 2 Interventions

combined with azenosertib

Group III: Combination with carboplatin Experimental Treatment 2 Interventions

combined with azenosertib

Group IV: Combination with bevacizumab Experimental Treatment 2 Interventions

combined with azenosertib

Group V: Combination with PLD Experimental Treatment 2 Interventions

combined with azenosertib

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+

Published Research Related to This Trial

The study identified two distinct molecular subgroups of high-grade serous epithelial ovarian cancers (EOCs) based on gene expressions related to POSTN/TGFBI and ESR1/WT1, which are associated with significantly different overall survival rates (30 months vs. 49 months).

BRCA germline mutations were more common in the ESR1/WT1 subgroup, suggesting that this subgroup may have specific therapeutic targets and prognostic implications for treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

POSTN/TGFBI-associated stromal signature predicts poor prognosis in serous epithelial ovarian cancer. Karlan, BY., Dering, J., Walsh, C., et al.[2022]

The standard treatment for platinum-resistant ovarian cancer involves non-platinum chemotherapy, with weekly paclitaxel showing the greatest benefits, but overall response rates remain modest, highlighting the need for improved therapies.

Recent trials indicate that while combination treatments with antiangiogenics have improved outcomes, there is still a lack of reliable biomarkers to predict treatment response, emphasizing the importance of thoughtful clinical trial designs and the exploration of novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Eskander, RN., Moore, KN., Monk, BJ., et al.[2023]

The study identified the overexpression of the IL6-STAT3-HIF pathway in ovarian clear cell adenocarcinoma (OCCA) tumors, suggesting it as a potential therapeutic target, especially since this pathway is linked to poor outcomes in patients.

Two patients with chemotherapy-resistant OCCA showed significant clinical responses to sunitinib treatment, indicating that this drug may be a promising option for patients with this specific type of ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Anglesio, MS., George, J., Kulbe, H., et al.[2022]

In a study of 105 epithelial ovarian cancer (EOC) patients, genomic profiling revealed that 61.1% exhibited BRCAness, a specific genomic signature associated with certain treatment responses, while 38.8% did not, indicating distinct molecular subgroups that could guide targeted therapies.

The research identified specific gene amplifications, particularly CCNE1 and BRD4, in non-BRCAness EOC cases, suggesting that these genes could serve as new therapeutic targets for high-grade ovarian carcinoma, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histo-genomic stratification reveals the frequent amplification/overexpression of CCNE1 and BRD4 genes in non-BRCAness high grade ovarian carcinoma. Goundiam, O., Gestraud, P., Popova, T., et al.[2019]

In a study of 60 cases of serous ovarian carcinoma (SOC), high levels of Nanog, ZEB1, and EpCAM were found to be significantly associated with aggressive tumor characteristics, such as higher grade, lymph node metastasis, and advanced FIGO stage, indicating a more severe disease progression.

The up-regulation of Nanog and ZEB1 was linked to poorer responses to chemotherapy and shorter overall and disease-free survival, suggesting that these markers could help predict treatment outcomes and guide more personalized therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic Impact of NANOG, ZEB1, and EpCAM Biomarkers on Prognosis of Serous Ovarian Carcinoma. Ibrahim, HM., Abdelrahman, AE., Elsebai, E., et al.[2023]

Citations

1. ir.zentalis.com ir.zentalis.com/news-releases/news-release-details/zentalis-pharmaceuticals-shares-updated-clinical-data

Release Details In 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 ...

2. targetedonc.com targetedonc.com/view/azenosertib-shows-promising-efficacy-in-platinum-resistant-ovarian-cancer

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 ...

3. onclive.com onclive.com/view/azenosertib-monotherapy-appears-safe-and-effective-in-ovarian-cancer

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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05128825

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 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5513

Correlation of cyclin E1 expression and clinical outcomes ... Background: Azenosertib (ZN-c3) is a novel, selective, and orally bioavailable WEE1 inhibitor demonstrating single-agent antitumor activity.

6. ir.zentalis.com ir.zentalis.com/news-releases/news-release-details/zentalis-pharmaceuticals-provides-update-azenosertib-clinical

Zentalis Pharmaceuticals Provides Update on Azenosertib ... FDA has placed a partial clinical hold on ZN-c3-001, DENALI and TETON monotherapy studies of azenosertib. Monotherapy data to be presented ...