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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05593094




Registration number
NCT05593094
Ethics application status
Date submitted
17/10/2022
Date registered
25/10/2022
Date last updated
3/09/2024

Titles & IDs
Public title
A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors
Scientific title
A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors
Secondary ID [1] 0 0
ZN-A-1041-101-US
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
HER2-positive Breast Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZN-A-1041 50mg BID
Treatment: Drugs - ZN-A-1041 100mg BID
Treatment: Drugs - ZN-A-1041 200mg BID
Treatment: Drugs - ZN-A-1041 400mg BID
Treatment: Drugs - ZN-A-1041 600mg BID
Treatment: Drugs - ZN-A-1041 800mg BID
Treatment: Drugs - ZN-A-1041 1000mg BID
Treatment: Drugs - ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b
Treatment: Drugs - ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1b
Treatment: Drugs - ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1b
Treatment: Drugs - ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1c
Treatment: Drugs - ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1c
Treatment: Drugs - ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1c

Experimental: ZN-A-1041 50mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 50mg Bid, for 21days as one cycle

Experimental: ZN-A-1041 100mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 100mg Bid, for 21days as one cycle

Experimental: ZN-A-1041 200mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 200mg Bid, for 21days as one cycle

Experimental: ZN-A-1041 400mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 400mg Bid, for 21days as one cycle

Experimental: ZN-A-1041 600mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 600mg Bid, for 21days as one cycle

Experimental: ZN-A-1041 800mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 800mg Bid, for 21days as one cycle

Experimental: ZN-A-1041 1000mg - Phase 1a:

Subjects will be given ZN-A-1041 orally 1000mg Bid, for 21days as one cycle

Experimental: 1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv. - Phase 1b Arm1:

1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2)
2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Experimental: 1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. - Phase 1b Arm2:

1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2)
2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Experimental: 1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta - Phase 1b Arm3:

1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2)
2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Experimental: 1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv. - Phase 1c Arm1:

The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.

Experimental: 1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. - Phase 1c Arm2:

The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.

Experimental: 1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO - Phase 1c Arm3:

The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.


Treatment: Drugs: ZN-A-1041 50mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 100mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 200mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 400mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 600mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 800mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 1000mg BID
twice a day (BID) via oral administration

Treatment: Drugs: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b
ZN-A-1041: twice a day (BID) via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)

Treatment: Drugs: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1b
ZN-A-1041: twice a day (BID) via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)

Treatment: Drugs: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1b
ZN-A-1041: twice a day (BID) via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion

Treatment: Drugs: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1c
ZN-A-1041: twice a day (BID) via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)

Treatment: Drugs: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1c
ZN-A-1041: twice a day (BID) via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)

Treatment: Drugs: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1c
ZN-A-1041: twice a day (BID) via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Incidence of Treatment-Emergent Adverse Events of ZN-A-1041 as a monotherapy in Phase 1a
Timepoint [1] 0 0
23 days
Primary outcome [2] 0 0
The Incidence of Treatment-Emergent Adverse Events of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta
Timepoint [2] 0 0
21 days
Primary outcome [3] 0 0
RP2D Dose
Timepoint [3] 0 0
through study completion, an average of 1 year
Secondary outcome [1] 0 0
Plasma, urine and potentially CSF level of ZN-A-1041 and its main metabolites
Timepoint [1] 0 0
From baseline to Cycle 9 (each cycel is 21 days)
Secondary outcome [2] 0 0
Serum level of combination drugs in phase 1c
Timepoint [2] 0 0
through study completion, an average of 2 year
Secondary outcome [3] 0 0
Anti-drug antibodies (ADAs) evaluation in Phase 1c
Timepoint [3] 0 0
through study completion, an average of 2 year
Secondary outcome [4] 0 0
overall Response Rate (ORR)
Timepoint [4] 0 0
through study completion, an average of 2 year
Secondary outcome [5] 0 0
Progression free survival(PFS)
Timepoint [5] 0 0
through study completion, an average of 2 year

Eligibility
Key inclusion criteria
*

1. ECOG performance status of 0 to 1
2. HER2 positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence In Situ Hybridization (FISH) positive, or IHC (+++).
3. Phase 1a study will enroll patients with unresectable or metastatic HER2-positive advanced solid tumor.

For patients who have no brain metastases, the following criteria should be met:
1. Patients should be relapsed or refractory to existing therapy(ies) or have been intolerant of such therapies
2. Patients with HER2-positive breast cancer should have previously received Trastuzumab, Pertuzumab, Trastuzumab emtansine(T-DM1) and a taxane.
3. Patients with HER2-positive gastric cancer must have previously received trastuzumab.
4. Have measurable or non-measurable disease assessable by RECIST 1.1.

For patients with brain metastasis, the following criteria should be met:
1. Patients with HER2-positive breast cancer must have received prior treatment with Trastuzumab, Pertuzumab and T-DM1, and a taxane or patient declined the above treatment.
2. Patients with HER2-positive gastric cancer must have previously received Trastuzumab
3. Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT and 2 weeks from SRS; ii) Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.

For patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks.
4. Phase 1b and Phase 1c study will enroll patients with unresectable locally advanced or metastatic HER2+ breast cancer.

For Phase 1b patients who have no brain metastases, the following criteria should be met:
1. For arm 1 and arm 2, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression.
2. Have measurable or non-measurable disease assessable by RECIST 1.1

For Phase 1c patients who have no brain metastases, the following criteria should be met:
1. For arm 1 and arm 2, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received a pertuzumab plus trastuzumab or T-DXd for advanced HER2+breast cancer with no evidence of disease progression.
2. In arms 1 and 2, patients should have at least one measurable lesion either extracranially or intracranially per RECIST v1.1.

For patients with brain metastasis, the following criteria should be met:
1. For arm 1 and arm 2 of phase 1b, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression. For arm 1 and arm 2 of phase 1c, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received previous treatment with a pertuzumab plus trastuzumab or T-DXd for advanced HER2+ breast cancer with no evidence of disease progression (except brain metastases).
2. Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT, 2 weeks from SRS and 4 weeks from surgery; ii) Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.
5. Suspected or confirmed leptomeningeal metastasis are allowed.
6. In Phase 1b arm1 and arm2, patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks. For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO and taxane.
7. In Phase 1c arm1 and arm2, Patients should not have received prior treatment with tucatinib, afatinib, or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for = 21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for = 21 days and was discontinued for reasons other than disease progression or severe toxicity). For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO or T-Dxd based induction.
*
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects who have participated in any clinical study or received any clinical study drug within 4 weeks prior to the first administration except for on-going Herceptin, Perjeta or PHESGO in arm3
2. CNS Exclusion - Based on screening brain MRI and clinical assessment

1. Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)
2. Any intracranial lesion thought to require immediate local therapy
3. Require antiepileptic treatment (except for these patients with stable seizures require continuous Levetiracetam therapy).
4. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/10/2026
Actual
Sample size
Target
210
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Andrew Love Cancer Center - Geelong
Recruitment hospital [2] 0 0
Sunshine Hospital - Australia - St Albans
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
France
State/province [7] 0 0
Nord
Country [8] 0 0
France
State/province [8] 0 0
Lyon
Country [9] 0 0
France
State/province [9] 0 0
Toulouse
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Spain
State/province [12] 0 0
Jaén
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Santiago de Compostela
Country [15] 0 0
Spain
State/province [15] 0 0
Sevilla
Country [16] 0 0
Spain
State/province [16] 0 0
Valencia
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Lancashire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Suzhou Zanrong Pharma Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anders Carey K, MD
Address 0 0
Duke Cancer Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ding Zhou, Ph.D
Address 0 0
Country 0 0
Phone 0 0
(86)-13916360900
Fax 0 0
Email 0 0
ding.zhou@zionpharma.com
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05593094