Trial Title:
A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors
NCT ID:
NCT05593094
Condition:
Advanced Solid Tumors
HER2-positive Breast Cancer
Conditions: Official terms:
Neoplasms
Trastuzumab
Pertuzumab
Ado-Trastuzumab Emtansine
Maytansine
Conditions: Keywords:
Phase 1
Advanced Solid Tumors
HER2 postive
Brain metastases
Herceptin
Perjeta
PHESGO
First Line
1st Line
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ZN-A-1041 50mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 50mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 100mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 100mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 200mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 200mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 400mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 400mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 600mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 600mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 800mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 800mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 1000mg BID
Description:
twice a day (BID) via oral administration
Arm group label:
ZN-A-1041 1000mg
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b
Description:
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)
Arm group label:
1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1b
Description:
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)
Arm group label:
1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1b
Description:
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
Arm group label:
1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1c
Description:
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)
Arm group label:
1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1c
Description:
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)
Arm group label:
1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.
Other name:
ZN-A-1041 Enteric Capsules
Intervention type:
Drug
Intervention name:
ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1c
Description:
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
Arm group label:
1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO
Other name:
ZN-A-1041 Enteric Capsules
Summary:
This will be a Phase 1, multicenter, open-label trial to evaluate the safety,
tolerability, PK and efficacy of ZN-A-1041 as a monotherapy or in combination in patients
with HER2-positive advanced solid tumors with or without brain metastases.
The study will consist of three phases: Phase 1a (dose escalation with ZN-A-1041
monotherapy), Phase 1b (dose escalation with ZN-A-1041 combination therapy) and Phase 1c
(dose expansion with ZN-A-1041 combination therapy).
Detailed description:
Phase 1a of the study will adopt the "modified 3+3" dose escalation design with a total
of 7 planned dose levels. Patients with HER2-positive advanced solid tumor (including
those with brain metastases) will be enrolled to receive a single-dose administration of
ZN-A-1041 followed by multiple-dose administration of ZN-A-1041.Phase 1b of the study
will adopt the "traditional 3+3" dose escalation design. The dose levels will be based on
the results of the Phase 1a study and the results of a food effect study. In Phase 1b,
patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and
without brain metastasis will be enrolled in three arms: Arm1 will receive multiple doses
of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in
combination with T-DXd. Arm 3 will receive multiple doses of ZN-A-1041 in combination
with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta and 4-8-cycle
treatment of taxane. Patients will be assessed for an appropriate arm by the sponsor and
the investigator at the time of consent. Patients with unresectable locally-advanced or
metastatic HER2+ breast cancer with and without brain metastasis are planned to be
enrolled in Phase 1c of the study: Arm1 will receive multiple doses of ZN-A-1041 in
combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with
T-DXd; Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or
Herceptin plus Perjeta after Herceptin plus Perjeta or T-DXd based induction regimen.
Patients will be assessed for an appropriate arm by the sponsor and the investigator at
the time of consent. Arm1 of Phase 1c can start independently after the DLT observation
period of the last patient in Phase 1b Arm1. Arm 2 of Phase 1c can start independently
after the DLT observation of the last patient in Phase 1b Arm 2. Arm 3 of Phase 1c can
start independently after the DLT observation of the last patient in Phase 1b Arm 3. The
dose levels used in Phase 1c will be based on the recommended doses obtained from the
Phase 1b study.
Each phase of the study includes a screening period (from 28 days prior to the first
administration of the study drug), a treatment period (until there are no clinical
benefits as deemed by the Investigator, disease progression, death, intolerable toxicity,
withdrawal of informed consent, loss of follow-up, or the start of new anti-tumor
treatment), and a follow-up period (until 28 days after the last administration of the
study drug). During the trial, the safety, tolerability, PK and efficacy data of
ZN-A-1041 as monotherapy and in combination in the subjects will be collected and
analyzed, thereby providing RP2D for subsequent future clinical trials.
Criteria for eligibility:
Criteria:
- 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.
- 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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
ACRC/Arizona Clinical Research Center, Inc
Address:
City:
Tucson
Zip:
85715
Country:
United States
Status:
Recruiting
Contact:
Last name:
Plezia PharmD
Phone:
520-290-2510
Email:
pplezia@acrcresearch.com
Investigator:
Last name:
Manuel R Modiano, MD
Email:
Principal Investigator
Facility:
Name:
TOI Clinical Research
Address:
City:
Cerritos
Zip:
90703-2684
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nawid Sarwari
Investigator:
Last name:
Nawid Sarwari
Email:
Principal Investigator
Facility:
Name:
Innovative Clinical Research Institute
Address:
City:
Whittier
Zip:
90603
Country:
United States
Status:
Recruiting
Contact:
Last name:
Leslie Posadas
Phone:
562-693-4477
Email:
leslieposadas@theoncologyinstitute.com
Investigator:
Last name:
Arati Chand, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Insitute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Olivia Postel
Phone:
877-338-7425
Email:
OliviaG_Postel@DFCI.HARVARD.EDU
Investigator:
Last name:
Nancy Lin, MD
Email:
Principal Investigator
Facility:
Name:
Barbara Ann Karmanos Cancer center
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hadeel Assad, MD
Phone:
313-576-8716
Email:
Assadh@karmanos.org
Investigator:
Last name:
Hadeel Assad, MD
Email:
Principal Investigator
Facility:
Name:
Duke Cancer Institute
Address:
City:
Durham
Zip:
27710
Country:
United States
Status:
Recruiting
Contact:
Last name:
JoAnna Gontarz
Phone:
919-684-6342
Email:
joanna.gontarz@duke.edu
Investigator:
Last name:
Carey Anders, MD
Email:
Principal Investigator
Facility:
Name:
Md Anderson Cancer center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rashmi Murthy, MD
Phone:
713-792-2817
Email:
RMurthy1@mdanderson.org
Investigator:
Last name:
Rashmi Murthy, MD
Email:
Principal Investigator
Facility:
Name:
Andrew Love Cancer Center
Address:
City:
Geelong
Zip:
3220
Country:
Australia
Status:
Active, not recruiting
Facility:
Name:
Sunshine Hospital - Australia
Address:
City:
St Albans
Zip:
3021
Country:
Australia
Status:
Active, not recruiting
Facility:
Name:
Centre Oscar Lambret - PPDS
Address:
City:
Lille
Zip:
59000
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Address:
City:
Lyon
Zip:
69373
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Institut Claudius Regaud - PPDS
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Auckland City Hospital
Address:
City:
Auckland
Zip:
1023
Country:
New Zealand
Status:
Active, not recruiting
Facility:
Name:
Instituto Oncologico Dr. Rosell-Hospital Universitari Dexeus-Grupo Quironsalud
Address:
City:
Barcelona
Zip:
8028
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Hospital Clinic de Barcelona
Address:
City:
Barcelona
Zip:
8036
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Hospital Universitario de Jaen
Address:
City:
Jaén
Zip:
23007
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Hospital Universitario Ramon y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Noelia Martínez Jáñez
Investigator:
Last name:
Noelia Martínez Jáñez
Email:
Principal Investigator
Facility:
Name:
Hospital Clinico San Carlos
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Hospital Clinico Universitario de Santiago
Address:
City:
Santiago de Compostela
Zip:
15706
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Hospital Universitario Virgen Macarena
Address:
City:
Sevilla
Zip:
41009
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Fundacion Instituto Valenciano de Oncologia
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Angel Luis Guerrero-Zotano
Investigator:
Last name:
Angel Luis Guerrero-Zotano
Email:
Principal Investigator
Facility:
Name:
The Christie - PPDS
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Active, not recruiting
Start date:
October 15, 2020
Completion date:
October 30, 2026
Lead sponsor:
Agency:
Suzhou Zanrong Pharma Limited
Agency class:
Industry
Source:
Suzhou Zanrong Pharma Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05593094
