ZN-c3 for Ovarian Cancer

Recruiting at 13 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

Trial Summary

What is the purpose of this trial?

This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of ZN-c3 in combination with other drugs.

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.

What data supports the effectiveness of the drug ZN-c3, Azenosertib, for ovarian cancer?

The research highlights the challenges in treating platinum-resistant ovarian cancer and suggests that novel treatments, including those targeting specific genetic changes, may offer promising results. Although ZN-c3, Azenosertib is not directly mentioned, the focus on new therapies and genetic targets in ovarian cancer suggests potential for drugs like ZN-c3, which may work on similar principles. ^{1 2 3 4 5}

Research Team

Philippe Pultar, MD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. [2022]

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

POSTN/TGFBI-associated stromal signature predicts poor prognosis in serous epithelial ovarian cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. [2023]

4. United States 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. [2019]

5. Thailand pubmed.ncbi.nlm.nih.gov

Clinicopathologic Impact of NANOG, ZEB1, and EpCAM Biomarkers on Prognosis of Serous Ovarian Carcinoma. [2023]