Phase
Condition
Neoplasms
Treatment
ZN-A-1041 200mg BID
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b
ZN-A-1041 400mg BID
Clinical Study ID
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
- Inclusion Criteria:
ECOG performance status of 0 to 1
HER2 positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence InSitu Hybridization (FISH) positive, or IHC (+++).
Phase 1a study will enroll patients with unresectable or metastaticHER2-positive advanced solid tumor.For patients who have no brain metastases, the following criteria should bemet:
Patients should be relapsed or refractory to existing therapy(ies) or havebeen intolerant of such therapies
Patients with HER2-positive breast cancer should have previously receivedTrastuzumab, Pertuzumab, Trastuzumab emtansine(T-DM1) and a taxane.
Patients with HER2-positive gastric cancer must have previously receivedtrastuzumab.
Have measurable or non-measurable disease assessable by RECIST 1.1.For patients with brain metastasis, the following criteria should be met:
Patients with HER2-positive breast cancer must have received priortreatment with Trastuzumab, Pertuzumab and T-DM1, and a taxane or patientdeclined the above treatment.
Patients with HER2-positive gastric cancer must have previously receivedTrastuzumab
Do not require immediate local treatment during the trial period, and meeteither of the following two criteria: i) For patients who have receivedprevious local treatment (surgery, whole brain radiotherapy (WBRT) andstereotactic radiosurgery (SRS)) for brain metastases, stable orprogression of intracranial lesions is required. Interval from prior localtherapy could be 3 weeks from WBRT and 2 weeks from SRS; ii) Symptomaticor not, patient has not received previous local treatment (surgery orradiotherapy) for brain metastases as long as no local therapy is neededduring the trial period.For patients who have received previous tyrosine kinase inhibitor (TKI)treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), theinterval between the last treatment and the first administration of the studydrug in this trial should be at least 2 weeks.
Phase 1b and Phase 1c study will enroll patients with unresectable locallyadvanced or metastatic HER2+ breast cancer.For Phase 1b patients who have no brain metastases, the following criteriashould be met:
For arm 1 and arm 2, patients should be relapsed or refractory to existingtherapy(ies), with a history of prior treatment with trastuzumab and ataxane. For arm3, patients have received 4-8 cycles (21-day cycles) ofprevious treatment with trastuzumab, pertuzumab, and taxane as first-linetherapy for advanced HER2+ breast cancer with no evidence of diseaseprogression.
Have measurable or non-measurable disease assessable by RECIST 1.1For Phase 1c patients who have no brain metastases, the following criteriashould be met:
For arm 1 and arm 2, patients should be refractory to existingtherapy(ies), with a history of prior treatment with trastuzumab. Forarm3, patients have received a pertuzumab plus trastuzumab or T-DXd foradvanced HER2+breast cancer with no evidence of disease progression.
In arms 1 and 2, patients should have at least one measurable lesioneither extracranially or intracranially per RECIST v1.1.For patients with brain metastasis, the following criteria should be met:
For arm 1 and arm 2 of phase 1b, patients should be relapsed or refractoryto existing therapy(ies), with a history of prior treatment withtrastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, andtaxane as first-line therapy for advanced HER2+ breast cancer with noevidence of disease progression. For arm 1 and arm 2 of phase 1c, patientsshould be refractory to existing therapy(ies), with a history of priortreatment with trastuzumab. For arm3, patients have received previoustreatment with a pertuzumab plus trastuzumab or T-DXd for advanced HER2+breast cancer with no evidence of disease progression (except brainmetastases).
Do not require immediate local treatment during the trial period, and meeteither of the following two criteria: i) For patients who have receivedprevious local treatment (surgery, whole brain radiotherapy (WBRT) andstereotactic radiosurgery (SRS)) for brain metastases, stable orprogression of intracranial lesions is required. Interval from prior localtherapy could be 3 weeks from WBRT, 2 weeks from SRS and 4 weeks fromsurgery; ii) Symptomatic or not, patient has not received previous localtreatment (surgery or radiotherapy) for brain metastases as long as nolocal therapy is needed during the trial period.
Suspected or confirmed leptomeningeal metastasis are allowed.
In Phase 1b arm1 and arm2, patients who have received previous tyrosine kinaseinhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration ofthe study drug in this trial should be at least 2 weeks. For arm3, patientsshould not have prior treatment for unresectable locally-advanced or metastaticHER2+ breast cancer with and without brain metastasis, except for ongoingHerceptin, Perjeta or PHESGO and taxane.
In Phase 1c arm1 and arm2, Patients should not have received prior treatmentwith tucatinib, afatinib, or any other investigational anti-HER2, anti-EGFR, orHER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months ofstarting study treatment (except in cases where they were given for ≤ 21 daysand was discontinued for reasons other than disease progression or severetoxicity). Prior treatment with pyrotinib for recurrent of mBC (except in caseswhere pyrotinib was given for ≤ 21 days and was discontinued for reasons otherthan disease progression or severe toxicity). For arm3, patients should nothave 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.
Exclusion
- Exclusion Criteria:
Subjects who have participated in any clinical study or received any clinicalstudy drug within 4 weeks prior to the first administration except for on-goingHerceptin, Perjeta or PHESGO in arm3
CNS Exclusion - Based on screening brain MRI and clinical assessment
Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)
Any intracranial lesion thought to require immediate local therapy
Require antiepileptic treatment (except for these patients with stableseizures require continuous Levetiracetam therapy).
Ongoing use of systemic corticosteroids for control of symptoms of brainmetastases at a total daily dose of > 2 mg of dexamethasone (orequivalent)
Study Design
Study Description
Connect with a study center
Andrew Love Cancer Center
Geelong, Victoria 3220
AustraliaSite Not Available
Sunshine Hospital - Australia
St Albans, Victoria 3021
AustraliaSite Not Available
Centre Oscar Lambret - PPDS
Lille, Nord 59000
FranceSite Not Available
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Lyon, 69373
FranceSite Not Available
Institut Claudius Regaud - PPDS
Toulouse, 31059
FranceSite Not Available
Auckland City Hospital
Auckland, 1023
New ZealandSite Not Available
Hospital Clinic de Barcelona
Barcelona, 8036
SpainSite Not Available
Instituto Oncologico Dr. Rosell-Hospital Universitari Dexeus-Grupo Quironsalud
Barcelona, 8028
SpainSite Not Available
Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
Barcelona, 8035
SpainSite Not Available
Hospital Universitario de Jaen
Jaén, 23007
SpainSite Not Available
Hospital Clinico San Carlos
Madrid, 28040
SpainSite Not Available
Hospital Universitario Ramon y Cajal
Madrid, 28034
SpainActive - Recruiting
Hospital Clinico Universitario de Santiago
Santiago de Compostela, 15706
SpainSite Not Available
Hospital Universitario Virgen Macarena
Sevilla, 41009
SpainSite Not Available
Fundacion Instituto Valenciano de Oncologia
Valencia, 46026
SpainActive - Recruiting
The Christie - PPDS
Manchester, Lancashire M20 4BX
United KingdomSite Not Available
ACRC/Arizona Clinical Research Center, Inc
Tucson, Arizona 85715
United StatesActive - Recruiting
TOI Clinical Research
Cerritos, California 90703-2684
United StatesActive - Recruiting
Innovative Clinical Research Institute
Whittier, California 90603
United StatesActive - Recruiting
Dana-Farber Cancer Insitute
Boston, Massachusetts 02215
United StatesActive - Recruiting
University of Michigan
Ann Arbor, Michigan 48109
United StatesSite Not Available
Barbara Ann Karmanos Cancer center
Detroit, Michigan 48201
United StatesActive - Recruiting
Duke Cancer Institute
Durham, North Carolina 27710
United StatesActive - Recruiting
Md Anderson Cancer center
Houston, Texas 77030
United StatesActive - Recruiting
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