ZN-c3 for Serous Carcinoma

(DENALI Trial)

Recruiting at 99 trial locations

Overseen By Project Director

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: K-Group Beta

Must be taking: Bevacizumab, PARP inhibitors, Mirvetuximab

Must not be taking: CYP3A inhibitors, P-gp inhibitors

Disqualifiers: Platinum-refractory, Unstable brain metastases, Heart failure, 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: Up to approximately 12 months

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called azenosertib (ZN-c3) to evaluate its effectiveness and safety for individuals with specific types of ovarian cancer that resist typical platinum-based treatments. Researchers focus on patients whose tumors test positive for a protein called Cyclin E1. The study explores different doses of the drug to determine the most effective one. Suitable candidates for this trial have high-grade serous ovarian, fallopian tube, or primary peritoneal cancer that hasn't responded to previous treatments like chemotherapy and have Cyclin E1 positive tumors. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking any drugs or supplements that are strong or moderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 days before starting the study. If you're on these medications, you may need to stop them.

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

Research has shown that azenosertib (ZN-c3) is generally safe for people. In one study, patients with ovarian cancer took azenosertib, and about one-third experienced a positive effect. Another study found that azenosertib helped control the disease in 90.9% of uterine cancer patients, highlighting the drug's potential to manage the condition.

Safety information from these studies suggests that azenosertib is usually well-tolerated, with most side effects being manageable. However, like any treatment, some risks exist. Participants should discuss these risks with their healthcare providers before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for serous carcinoma?

Researchers are excited about ZN-c3, also known as Azenosertib, because it targets serous carcinoma in a unique way. Unlike standard chemotherapy treatments like carboplatin and paclitaxel, which attack all rapidly dividing cells, ZN-c3 specifically inhibits a protein crucial for cancer cell division. This targeted approach may lead to fewer side effects and improved outcomes. Additionally, Azenosertib's intermittent dosing schedule of 5 days on, 2 days off could optimize its effectiveness while minimizing toxicity, offering a promising new option for patients with this challenging cancer.

What evidence suggests that ZN-c3 might be an effective treatment for serous carcinoma?

Research has shown that azenosertib (ZN-c3) may help treat certain cancers, such as ovarian cancer. In earlier studies, about 35% of patients with platinum-resistant ovarian cancer experienced tumor shrinkage with this treatment, meaning roughly one in three patients saw positive results. Azenosertib also demonstrated similar results in patients with various solid tumors, with benefits lasting over five months on average. These findings suggest that azenosertib could be effective for hard-to-treat cancers, especially for those with platinum-resistant high-grade serous ovarian cancer. Overall, azenosertib has been well-tolerated and has shown the ability to fight tumors on its own in different types of cancer.

In this trial, participants will receive azenosertib at different dosages to further evaluate its effectiveness and safety. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who've had up to three prior treatments including bevacizumab. They must have a measurable lesion and an ECOG performance status of ≤1. Participants need to agree to contraception use during and after the trial for specified periods.

Inclusion Criteria

My condition did not improve with platinum-based chemotherapy.

Measurable disease per RECIST Version 1.1

I have high-grade serous ovarian cancer.

Exclusion Criteria

I have not had radiation therapy in the last 3 weeks.

I don't have serious illnesses like recent bowel blockages or need for frequent fluid removal.

I haven't had chemotherapy or targeted therapy in the last 14 days or 5 half-lives, whichever is shorter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Azenosertib on a 5 days on, 2 days off intermittent schedule

Up to approximately 12 months

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's effectiveness, safety, how it moves through the body (pharmacokinetics), and its impact on certain biomarkers in patients with specific types of advanced gynecological cancers that have worsened within six months despite treatment.

How Is the Trial Designed?

Group I: Part 2b Experimental Treatment 1 Intervention

Azenosertib at the dose selected in Part 2a administered on a 5 days on, 2 days off intermittent schedule

Group II: Part 2a: Arm 2 Experimental Treatment 1 Intervention

Azenosertib 300mg administered on a 5 days on, 2 days off intermittent schedule

Group III: Part 2a: Arm 1 Experimental Treatment 1 Intervention

Azenosertib 400mg administered on a 5 days on, 2 days off intermittent schedule

Group IV: Part 1a/1b (Completed Enrollment) Experimental Treatment 1 Intervention

Azenosertib 400mg administered on a 5 days on, 2 days off intermittent schedule.

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 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]

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]

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/azenosertib-monotherapy-appears-safe-and-effective-in-ovarian-cancer

Azenosertib Monotherapy Appears Safe and Effective in ... Azenosertib (ZN-c3) monotherapy elicited an overall response rate (ORR) of 34.9% (95% CI, 21.0%-50.9%) in response-evaluable, ...

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

Azenosertib Shows Promising Efficacy in Platinum- ... Single-agent azenosertib (ZN-c3) generated an overall response rate (ORR) of 34.9% (95% CI, 21.0%-50.9%) among the 43 response-evaluable, ...

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

Zentalis Pharmaceuticals Provides Update on Azenosertib ... In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04158336

A Study of ZN-c3 in Participants With Solid Tumors 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 at a total daily ...

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. 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%.

8. 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 ...