Phase 2 Study of ZN‑c3 in High-Grade Serous Ovarian Cancer

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

31 Jul 2025 → ongoing

Decision date (initial)

2024-02-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

K-Group Beta, Inc.

External identifiers

EU CT number

2022-502983-19-00

ClinicalTrials.gov

NCT05128825

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Part 1b:
• To determine the safety and tolerability of azenosertib in subjects with PROC
Part 2a:
• To investigate the antitumor activity of 2 dose levels of azenosertib in subjects with cyclin E1-positive PROC
• To investigate the safety and tolerability of 2 dose levels of azenosertib in subjects with cyclin E1-positive PROC

Part 2b:
• To investigate the antitumor activity of azenosertib in subjects with cyclin E1-positive PROC at the selected dose

Secondary objectives 3

1. Part 1b: • To investigate the antitumor activity of azenosertib in subjects with PROC at different doses/schedules • To investigate the plasma PK of azenosertib
2. Part 2a: • To further investigate the antitumor activity of 2 dose levels of azenosertib in subjects with PROC • To investigate the antitumor activity of 2 dose levels of azenosertib in subgroups of enrolled subjects with and without detectable CCNE1 gene amplification status, as determined by central assay • To characterize the PK profile of 2 dose levels of azenosertib in subjects with cyclin E1-positive PROC
3. Part 2b: • To investigate the safety and tolerability of azenosertib in subjects with cyclin E1-positive PROC • To further investigate the antitumor activity of azenosertib in enrolled subjects with cyclin E1-positive PROC • To further investigate the antitumor activity of azenosertib in subgroups of enrolled subjects with and without detectable CCNE1 gene amplification status, as determined by central assay

Conditions and MedDRA coding

High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Provision of signed ICF
2. 2. Female Age ≥18 years (or age of majority in local region) at the time of informed consent.
3. 3. Histologically or cytologically confirmed recurrent, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer
4. 4. Subject must have platinum-resistant disease
5. 5. Subjects must have received 1-3 prior lines of therapy (up to 4 if prior mirvetuximab) for Part 2 (up to 4 if prior mirvetuximab)
6. 6. Prior mirvetuximab is required if approved and available for eligible subjects
7. 7. Subjects must have at least one measurable lesion as defined by RECIST Guideline Version 1.1
8. 8. Performance Status: Eastern Cooperative Oncology Group (ECOG) score of ≤1.
9. 9. Adequate hematologic and organ function during the Screening Period For the complete Inclusion Criteria, please refer to the study protocol

Exclusion criteria 5

1. 1. Platinum refractory disease (in front line therapy)
2. 2. Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1 (C1D1): a. Hospitalization for any reason within 14 days c. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter); d. Radiation therapy within 21 days; however, if the radiation portal covered ≤5% of the bone marrow, the subject is eligible irrespective of the end date of radiotherapy. e. Autologous or allogeneic stem cell transplant within 3 months. f. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
3. 3. Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or PKMYT1 inhibitor.
4. 4. A serious illness or medical conditions, listed in study protocol, including:
5. 6. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation). For the complete Exclusion Criteria, please refer to the study protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1b: • Frequency and severity of TEAEs • Incidence of dose interruptions, dose reductions, and permanent discontinuations of ZN-c3 azenosertib due to related TEAEs
2. Part 2a: Independent primary endpoints: ORR as defined by RECIST v1.1 and as assessed by the Investigator in subjects with centrally determined cyclin E1-positive status • Frequency and severity of TEAEs
3. Part 2b: • ORR as defined by RECIST v1.1 and as assessed by ICR in subjects with centrally determined cyclin E1-positive status

Secondary endpoints 3

1. Part 1b: • Summarized by cohort and overall: o ORR, DOR, TTR, PFS, and CBR as defined by RECIST v1.1 and as assessed by ICR and the Investigator o OS o CA-125 response by GCIG criteria • Plasma concentrations of azenosertib
2. Part 2a: • DOR, TTR, PFS, and CBR as defined by RECIST v1.1 and as assessed by the Investigator • OS • CA-125 response by GCIG criteria • ORR and DOR as defined by RECIST v1.1 and as assessed by the Investigator • Systemic plasma concentrations of azenosertib
3. Part 2b: • Frequency and severity of TEAEs • ORR, DOR, TTR, PFS, and CBR as defined by RECIST v1.1 as assessed by the Investigator • DOR, TTR, PFS, and CBR as defined by RECIST v1.1 as assessed by ICR • OS • CA-125 response by GCIG criteria • ORR and DOR as defined by RECIST v1.1 as assessed by the Investigator

Investigational products

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

Test 2

Auxiliary 6

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 Medical Affairs

Public contact point

Organisation

K-Group Beta Inc.

Contact name

Head of Medical Affairs

Third parties 12

Locations

5 EU/EEA countries · 36 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 2 · Art. 38 CTR

Urgent safety measures 3 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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