Phase 1/2 Study of ZN-c3 and Niraparib and ZN-c3 Monotherapy in Platinum-Resistant 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

29 Sep 2022 → 20 Jan 2026

Decision date (initial)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

K-Group Beta, Inc.

External identifiers

EU CT number

2024-515196-35-00

EudraCT number

2021-004161-13

ClinicalTrials.gov

NCT05198804

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Pharmacokinetic, Dose response, Efficacy

ZN-c3 in combination with niraparib:
• Phase 1b: To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D
• Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib
ZN-c3 monotherapy:
• To determine the safety and tolerability of ZN-c3 monotherapy
• To investigate the antitumor activity of ZN-c3 monotherapy

Secondary objectives 1

1. "To further investigate the antitumor activity of ZN-c3 in combination with Niraparib and ZN-c3 monotherapy. -To investigate the overall survival (OS) of subjects receiving ZN-c3 in combination with Niraparib and ZN-c3 monotherapy. -To investigate the safety and tolerability of ZN-c3 in combination with Niraparib. -To evaluate changes in patient-reported outcomes (PRO) and quality of life for ZN-c3 in combination with Niraparib. -To investigate the plasma PK of ZN-c3 and Niraparib when given in combination and ZN-c3 monotherapy. "

Conditions and MedDRA coding

Platinum-Resistant Ovarian Cance

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically or cytologically confirmed recurrent high grade epithelial ovarian, primary peritoneal, or fallopian tube cancer with histologic subtypes of serous, clear cell or endometroid for which there is no known or established treatment available with curative intent.
2. Subjects must have platinum-resistant disease.
3. Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined as at least one lesion that can be accurately measured.
4. Adequate hematologic and organ function.
5. Ability and willingness to take oral medication.
6. Subjects must provide formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer.

Exclusion criteria 9

1. Major surgery within 28 days (any surgical incision should be fully healed prior to study drug administration).
2. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter)
3. A minimum of 10 days between termination of the prior PARPi and administration of ZN-c3 and niraparib treatment is required.
4. Any investigational drug therapy <28 days.
5. Prior treatment with a WEE1 inhibitor.
6. Known hypersensitivity to any drugs similar to ZN-c3 and/or niraparib in class or its excipients.
7. Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
8. Uncontrolled hypertension (Diastolic BP > 90 mmHg or Systolic BP > 140 mmHg).
9. Myocardial impairment of any cause (e.g., cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV). Significant gastrointestinal abnormalities, requirement for IV alimentation, active peptic ulcer, chronic diarrhea, or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. ZN-c3 with niraparib: • Phase 1: Frequency and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 (C1).
2. • Phase 2: – Stage 1 (Futility): Progression-free survival (PFS) at 4 months as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1. – Stage 2 (Promising Clinical Activity): Objective response rate (ORR) as defined by the revised RECIST Guideline version 1.1 and assessed by Independent Central Review (ICR).
3. ZN-c3 monotherapy: • Frequency and severity of adverse events (AEs), including laboratory abnormalities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. • Incidence of dose interruptions, dose reductions, and permanent treatment discontinuations due to treatment-related AEs • ORR as defined by the revised RECIST Guideline version 1.1 and assessed by ICR.

Secondary endpoints 8

1. • Duration of response (DOR) as a key secondary endpoint
2. Clinical benefit rate (CBR), PFS (median and 4-month rate), as defined by the revised RECIST Guideline version 1.1.
3. ORR based on Investigator assessment using RECIST v 1.1
4. OS (median at 12 months and overall)
5. Frequency and severity of AEs, including laboratory abnormalities, graded according to the NCI-CTCAE version 5.0.
6. Incidence of dose interruptions, dose reductions, and permanent treatment discontinuations due to treatment-related AEs
7. Ongoing measurement of subject-reported symptomatic toxicity according to the PRO-CTCAE, and determination of change from Baseline in self-reported quality of life using EQ-5D-5L
8. Plasma PK parameters of ZN-c3 (and its potential metabolites, as applicable) and niraparib.

Investigational products

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

Test 2

Comparator 1

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

Head of Regulatory Affairs

Third parties 12

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 31 files

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

Application history

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