A Study of ZN-c3 in Women With Recurrent or Persistent Uterine Serous Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

K-Group Beta Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 May 2024 → 24 Oct 2025

Decision date (initial)

2024-03-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

K-Group Beta, Inc.

External identifiers

EU CT number

2023-507324-23-00

ClinicalTrials.gov

NCT04814108

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Part 1b:
• To determine the safety and tolerability of ZN-c3 in subjects with recurrent or persistent USC
Part 2:
• To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC

Secondary objectives 2

1. Part 1b: • To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules • To investigate the plasma PK of ZN-c3
2. Part 2: • To further investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC • To investigate the safety and tolerability of ZN-c3 in subjects with recurrent or persistent USC • Association of key biomarkers with clinical outcome of ZN-c3 activity • To investigate the plasma PK of ZN-c3

Conditions and MedDRA coding

recurrent or persistent uterine serous carcinoma

Study design 4 periods

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Provision of signed informed consent prior to initiation of any study related procedures 2. Females ≥18 years old 3. Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject • Endometrial carcinoma of mixed histology where the serous component ≥ 5% of the tumor • Carcinosarcomas (even with a serous component) are not eligible 4. ECOG PS 0 or 1
2. 5. Measurable disease per RECIST 1.1 criteria that has not been previously irradiated or has progressed following radiation therapy 6. Required prior therapy for endometrial cancer: • platinum-based chemotherapy regimen • PD-(L)1 inhibitor, except for subjects who are not clinically eligible in the opinion of the Investigator, or in regions where it is unavailable. • Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible in the opinion of the Investigator, or in regions where it is unavailable 7. FFPE tumor tissue block collected within 3 years prior to ICF
3. 8. Adequate hematologic and organ function during the Screening period, as defined: • ANC ≥1.5 × 109/L • Hgb ≥9.0 g/dL without PRBC transfusion in the prior 14 days • Platelet count ≥100 × 109/L • ALT and aspartate aminotransferase AST ≤3 × ULN;AST and ALT ≤5 × ULN if abnormalities are due to liver metaseses • Total serum bilirubin ≤1.5 × ULN or ≤3 × ULN in the case of Gilbert’s Syndrome • CrCl ≥30 mL/min based on Cockcroft-Gault method 9. Females of childbearing potential must agree to use an effective method of contraception prior to the first dose and for at least 6 months after the last dose of ZN c3. For determination of effective methods of contraception, refer to Section 12.1 10. Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion criteria 3

1. 1. Any of the following treatment interventions within the specified time frame prior to C1D1: • Major surgery within 28 days and any preplanned major surgery during the study treatment period. • Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter). • Radiation within 21 days. • Autologous or allogeneic stem cell transplant within 3 months. • Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter) • Inability to discontinue treatment with drugs, or to discontinue food and herbal supplements, that are strong or moderate CYP3A inhibitors and inducers, or P-gp inhibitors at least 14 days prior to start of study drug treatment. Mandatory anti-emetics that may be CYP3A inhibitors are an exception to this criterion 2. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor 3. Known hypersensitivity to ZN-c3 or any of the inactive ingredients in ZN-c3
2. 4. A serious illness or medical condition(s) including, but not limited to, the following: • Brain metastases that require immediate treatment or are clinically or radiologically unstable • Leptomeningeal disease that requires or is anticipated to require immediate treatment • Myocardial impairment of any cause resulting in heart failure by New York Heart Association Criteria (Class III or IV) • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study • Significant gastrointestinal abnormalities, considered to be clinically significant in the judgrior to C1D1, rement of the Investigator, or prior surgical procedures affecting absorption • Active, uncontrolled systemic infection. • Any evidence of bowel obstruction , recent hospitalization for bowel obstruction within 3 months prior to C1D1, or paracentesis/ thoracentesis within 3 weeks pcurrent paracentesis or thoracentesis within 6 weeks prior to C1D1 5, or paracentesis/thoracentesis anticipated during C1. Unresolved toxicity of Grade >1 attributed to any prior therapies
3. 6. Pregnant or lactating females or females of childbearing potential who have a positive serum pregnancy test within 14 days prior to C1D1 7. History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free. 8. Individuals who are judged by the Investigator to be unsuitable as study subjects

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1b: • Frequency and severity of TEAEs, including laboratory abnormalities, graded according to the NCI-CTCAE v5.0 • Incidence of dose interruptions, dose reductions, and permanent discontinuations of ZN-c3 due to ZN-c3–related TEAEs
2. Part 2: • ORR as defined by the revised RECIST v1.1 as assessed by ICR

Secondary endpoints 2

1. Part 1b •ORR, DOR, PFS, CBR, and TTR as defined by the revised RECIST v1.1. •OS •Plasma PK concentrations of ZN-c3
2. Part 2 •DOR as defined by RECIST v1.1. and assessed by ICR •PFS, CBR, and TTR as defined by RECIST v1.1. and assessed by ICR •ORR, PFS, CBR, and TTR as defined by RECIST v1.1. and assessed by the Investigator •OS •Frequency and severity of TEAEs •Association of key biomarkers with clinical outcome of ZN-c3 activity •Plasma PK concentrations of ZN-c3

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

K-Group Beta Inc.

Sponsor organisation

K-Group Beta Inc.

Address

10275 Science Center Drive Suite 200b

City

San Diego

Postcode

92121-1117

Country

United States

Scientific contact point

Organisation

K-Group Beta Inc.

Contact name

Head of Regulatory Affairs

Public contact point

Organisation

K-Group Beta Inc.

Contact name

Medical Affairs

Third parties 12

Locations

3 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Urgent safety measures 3 · Art. 54 CTR

Application history

2 submissions — initial application plus substantial / non-substantial modifications