ZN-c3 for Uterine Cancer

Recruiting at 74 trial locations

Overseen By Project Director

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: K-Group Beta

Must be taking: Platinum-based, PD-(L)1 inhibitors, HER2-targeted

Must not be taking: WEE1 inhibitors, ATR inhibitors

Disqualifiers: Bowel obstruction, Carcinosarcomas, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

76 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) to evaluate its effectiveness and safety for women with uterine serous carcinoma (USC). The focus is on women whose cancer has returned or persisted after other treatments. Participants should have previously tried therapies such as platinum-based chemotherapy and a PD-(L)1 inhibitor and must have measurable disease. For those diagnosed with USC and lacking other effective treatment options, this trial might be worth considering. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have had chemotherapy, targeted tumor therapy, or investigational drug therapy within a certain time frame before starting the trial.

Is there any evidence suggesting that ZN-c3 is likely to be safe for humans?

Research has shown that ZN-c3, also known as azenosertib, is generally safe and well-tolerated. Studies have found it helps control the disease in 90.9% of patients with advanced uterine cancer, preventing the disease from worsening in most cases. Additionally, ZN-c3 has shown promising results in other difficult-to-treat solid tumors, with some patients experiencing significant improvements.

However, some concerns exist. In another study involving this drug for different solid tumors, two deaths related to infections occurred, leading to a temporary pause in some trials. While such events are uncommon, they are important to consider.

Overall, ZN-c3 appears safe for most people, but like any treatment, it carries risks. Always discuss potential side effects with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ZN-c3 for uterine cancer because it works differently from current treatments like chemotherapy and hormone therapy. ZN-c3, also known as azenosertib, is a novel oral treatment that targets a specific enzyme involved in cancer cell growth. This targeted approach may offer a more precise attack on cancer cells, potentially reducing side effects compared to traditional treatments. By focusing on this unique mechanism, ZN-c3 could provide a new option for patients who don't respond well to existing therapies.

What evidence suggests that ZN-c3 might be an effective treatment for uterine cancer?

Research has shown that ZN-c3 (azenosertib), the investigational treatment in this trial, may effectively treat uterine serous carcinoma, a type of uterine cancer. One study demonstrated that this treatment controlled the disease in 90.9% of participants, stabilizing cancer in nearly 91% of cases. It also reduced tumor size in 27.3% of patients, with over a quarter experiencing tumor shrinkage. Additionally, ZN-c3 proved to be safe and well-tolerated, making it a promising option for individuals with this condition. ^{2 3 6 7 8}

Who Is on the Research Team?

Project Director

Principal Investigator

K-Group Beta (A wholly owned subsidiary of Zentalis Pharmaceuticals)

Are You a Good Fit for This Trial?

This trial is for adult women with recurrent or persistent uterine serous carcinoma who are in good physical condition (ECOG PS of 0 or 1), have measurable disease, and proper organ function. Participants must be at least 18 years old and agree to use contraception. Women can't join if they've had certain prior treatments, other serious medical conditions, unresolved toxicities from past therapies, are pregnant/breastfeeding, have uncontrolled second cancers, or specific heart issues.

Inclusion Criteria

I am a woman aged 18 or older.

I am fully active or restricted in physically strenuous activity but can do light work.

My blood counts and organ functions are within normal ranges.

Exclusion Criteria

I have never been treated with ZN-c3 or any WEE1 inhibitor.

I have been treated with a cell cycle checkpoint inhibitor before.

12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of > 480 ms at screening, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZN-c3 (azenosertib) orally with food to evaluate clinical activity and safety

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ZN-c3

Trial Overview The study tests the effectiveness and safety of a drug called ZN-c3 (azenosertib) specifically in women with uterine serous carcinoma that has come back or hasn't gone away after treatment. It's a Phase 2 clinical trial focusing on how well this drug works against this type of cancer.

How Is the Trial Designed?

Group I: ZN-c3 Single Agent Experimental Treatment 1 Intervention

ZN-c3 (azenosertib) taken orally with food

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

ZKSCAN3 is significantly overexpressed in uterine cervical cancers compared to non-cancerous tissues, indicating its potential role as an oncoprotein in cancer development.

The overexpression of ZKSCAN3 is associated with poor overall survival in patients, suggesting it could serve as a valuable molecular marker for predicting prognosis and aiding in early detection of cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer. Lee, S., Cho, YE., Kim, JY., et al.[2019]

SLC39A4 is significantly upregulated in cervical squamous cell carcinoma and endocervical adenocarcinoma, and higher levels of this gene are associated with shorter overall survival, indicating its potential as a prognostic marker.

The study found that SLC39A4 plays a crucial role in tumor cell metastasis and proliferation, and its high expression correlates with poor responses to chemotherapy and radiation, suggesting it could be a target for new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of SLC39A4 in the prognosis, immune microenvironment, and contribution to malignant behavior in vivo and in vitro of cervical cancer. Zhao, YC., Wang, TJ., Cui, J., et al.[2023]

ZNF275 is found to be overexpressed in cervical cancer tissues compared to normal tissues, and its downregulation leads to reduced cell viability, migration, and invasion while promoting apoptosis in cervical cancer cells.

The combination of the AKT inhibitor triciribine and cisplatin shows enhanced therapeutic effects in cervical cancer models with high ZNF275 expression, leading to greater tumor regression than either treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of ZNF275/AKT Pathway in Carcinogenesis and Cisplatin Chemosensitivity of Cervical Cancer Using Patient-Derived Xenograft Models. Ye, M., Liu, T., Miao, L., et al.[2023]

ZC3H13 is crucial for the malignancy of cervical cancer (CC) by mediating N6-methyladenosine (m6A) modification, which stabilizes the expression of CKAP2, a protein associated with cancer progression.

Inhibiting ZC3H13 reduces CC cell proliferation, migration, and invasion, while promoting its expression enhances these malignant traits, indicating that targeting the ZC3H13-m6A-CKAP2 pathway could be a promising therapeutic strategy for cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZC3H13 Enhances the Malignancy of Cervical Cancer by Regulating m6A Modification of CKAP2. Zhang, Y., Chen, X., Chen, H., et al.[2023]

ZKSCAN3 is overexpressed in breast cancer tissues compared to normal tissues, and its high expression is associated with poor patient prognosis, indicating its potential as a biomarker for breast cancer severity.

Knocking down ZKSCAN3 in breast cancer cells significantly reduces cell viability, migration, and invasion, while also inhibiting the Akt/mTOR signaling pathway, suggesting that targeting ZKSCAN3 could be an effective therapeutic strategy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion. Chi, Y., Xu, H., Wang, F., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04814108

A Study of ZN-c3 in Women With Recurrent or Persistent ... This is a Phase 2 study to evaluate the clinical activity and safety of ZN-c3 (azenosertib) in adult women with recurrent or persistent uterine serous carcinoma ...

2. onclive.com onclive.com/view/zn-c3-shows-preliminary-efficacy-safety-in-recurrent-advanced-uterine-serous-carcinoma

ZN-c3 Shows Preliminary Efficacy, Safety in Recurrent ... The investigational Wee1 inhibitor ZN-c3 was found to be safe and to produce a disease control rate of 90.9% and an objective response rate of 27.3%.

3. onclive.com onclive.com/view/fda-places-partial-clinical-holds-on-3-trials-evaluating-azenosertib-in-advanced-solid-tumors

FDA Places Partial Clinical Holds on 3 Trials Evaluating ... The ZN-c3-001 trial showed a 37% ORR and 6.5 months median PFS in patients with platinum-resistant ovarian cancer and uterine serous carcinoma.

4. clinicaltrial.be clinicaltrial.be/en/details/45980?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

A Study of ZN-c3 in Women With Recurrent or Persistent Ut... This is a Phase 2 open-label, multicenter study to evaluate the clinical activity and safety of ZN-c3 (also known as azenosertib; ...

5. ir.zentalis.com ir.zentalis.com/news-releases/news-release-details/zentalis-pharmaceuticals-announces-promising-initial-data

Release Details ZN-c3 demonstrated single agent activity, generating Exceptional Responses in a range of heavily pre-treated solid tumors. ZN-c3 was safe and well-tolerated.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04814108

A Study of ZN-c3 in Women With Recurrent or Persistent ... This is a Phase 2 study to evaluate the clinical activity and safety of ZN-c3 (azenosertib) in adult women with recurrent or persistent uterine serous carcinoma ...

7. dana-farber.org dana-farber.org/clinical-trials/24-061

A Biomarker Study of the Wee1 inhibitor Azenosertib (ZN- ... This research study is being done to investigate how Azenosertib affects tumor cells of persistent or recurrent uterine serous carcinoma.

8. cancernetwork.com cancernetwork.com/view/fda-places-partial-holds-on-3-trials-for-solid-tumor-treatment-azenosertib

FDA Places Partial Holds on 3 Trials for Solid Tumor ... Two deaths due to presumed sepsis in patients treated in the DENALI trial led to the clinical holds on the advanced solid tumor treatment.