ZN-c3 for Serous Carcinoma

(DENALI Trial)

Recruiting at 68 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

Trial Summary

What is the purpose of this trial?

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, Fallopian Tube, or Primary Peritoneal Cancer. Part 2 of the study will be conducted in subjects whose tumors are Cyclin E1 positive as determined by central review using the Sponsor's investigational clinical trial assay.

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.

What makes the drug ZN-c3 (Azenosertib) unique for treating serous carcinoma?

ZN-c3 (Azenosertib) is unique because it targets specific proteins involved in cancer cell growth and survival, potentially offering a new approach for treating serous carcinoma, which lacks standard treatment options. This drug's mechanism of action may differ from existing therapies by focusing on molecular pathways not previously targeted in this type of cancer. ^{1 2 3 4 5}

Eligibility Criteria

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

Measurable disease per RECIST Version 1.1

My condition did not improve with platinum-based chemotherapy.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Zinc carnosine: Frontiers advances of supplement for cancer therapy. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self-Synergistic Tumor Targeting Therapy. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion. [2021]