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Trial registered on ANZCTR


Registration number
ACTRN12620000592943
Ethics application status
Approved
Date submitted
24/04/2020
Date registered
21/05/2020
Date last updated
21/05/2020
Date data sharing statement initially provided
21/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I Dose Finding Study in Patients with HER2-Positive Advanced Solid Tumors
Scientific title
A Phase 1, Open-Label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of GQ1001, a HER2 Antibody-Drug Conjugate, in Patients with HER-2 Positive Advanced Solid Tumors
Secondary ID [1] 301100 0
GQCT001
Secondary ID [2] 301119 0
GQ1001X2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-Positive Advanced Solid Tumors 317173 0
Condition category
Condition code
Cancer 315327 315327 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The name of the drug being administered is GQ1001. GQ1001 is an Antibody-Drug Conjugate used to treat patients with HER2-positive advanced solid tumors. GQ1001 will be administered by the licensed medical staff at the clinical site as a single intravenous dose on Day 1 of a 21-day treatment cycle. Patient medical records, routine safety lab tests and other necessary medical monitoring will be conducted by the investigators and site medical staff during the study.
Eligible patients will be enrolled into one specific dose cohort following the study progress. Intra-patient dose escalation will not be allowed. Dose cohorts planned for the dose escalation are 1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg, 4.8 mg/kg, and 6.0 mg/kg. Eight cycles treatment was planned for each enrolled patient. The safety review by the Safety Review Committee (SRC) will occur on a continual basis through the duration of the study. The SCR will monitor the safety and provide decisions as to dose escalations and exploring intermediate or higher doses. Patients may stay on the study treatment longer, until disease progression occurs, unacceptable toxicity occurs, or voluntarily withdraw the consent.
Intervention code [1] 317427 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323602 0
Dose Limiting Toxicities (DLTs). Adverse events will be assessed using NCI CTCAE version 5.0 and will be evaluated by the investigator and the sponsor for the eligibility of DLT.
Timepoint [1] 323602 0
End of Cycle 1 (21-day cycle)
Secondary outcome [1] 382332 0
Safety and tolerability. Safety and tolerability will be assessed by incidence and severity of adverse events (AEs) and/or by abnormal laboratory values, vital signs, ECGs, or ECOG performance status.

AEs will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Known/possible AEs and assessments include:
- neutropenia assessed by lab hematology assessment
- anemia assessed by lab hematology assessment
- thrombocytopenia assessed by lab hematology assessment
- heart failure assessed by ECG or Echocardiography
- left ventricular ejection fraction assessed by Echocardiography
- electrolyte abnormality assessed by blood biochemistry assessment
- increased bilirubin assessed by blood biochemistry assessment
- increased AST/ALT assessed by blood biochemistry assessment



Timepoint [1] 382332 0
Safety lab and AE assessment will be conducted weekly in the first cycle and at least every 3 weeks or more often in the following cycles.
Secondary outcome [2] 382698 0
Pharmacokinetic (PK) Parameters using plasma and serum assays
- AUC(0-last)
- Cmax
- Tmax
- T1/2
- MRT
- Vd
Timepoint [2] 382698 0
Cycle PK Collection Time Point
Screening
1 Pre-dose
1 EOI
1 30 min post-dose
1 2 h post-dose
1 8 h post-dose
1 24 h post-dose
1 48 h post-dose
1 72 h post-dose
1 168 h post-dose
1 336 h post-dose
2 Pre-dose
2 EOI
3 Pre-dose
3 EOI
3 30 min post-dose
3 2 h post-dose
3 8 h post-dose
3 24 h post-dose
3 48 h post-dose
3 72 h post-dose
3 168 h post-dose
3 336 h post-dose
4 Pre-dose
4 EOI
4 20 d post-dose
5 Pre-dose
6 Pre-dose
7 Pre-dose
8 Pre-dose

Secondary outcome [3] 382699 0
Preliminary efficacy as evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and CT or MRI scans.
Timepoint [3] 382699 0
RESIST assessments and CT or MRI scans will be performed at the baseline visit and every 9 weeks until the end of the study.

Eligibility
Key inclusion criteria
1. Patients who are voluntary to participate in this clinical study, able to understand the study procedure, and have signed the informed consent form.

2. Male or female 18 to 65 years of age.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening;

4. Has a life expectancy greater than or equal to 3 months;

5. Left ventricular ejection fraction (LVEF) greater than or equal to 50% by echocardiography within 28 days before registration;

6. Is willing to provide pre-existing diagnostic or resected tumor samples;

7. Patients must have pathologically documented advanced/unresectable or metastatic solid tumor with HER2 overexpression/expression (refer to the following definition) that is refractory to standard therapy or for which there is no standard available therapy:
- advanced/unresectable or metastatic breast cancer: IHC 3+ or IHC 2+/ISH* +; - Advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: IHC 3+ or IHC
2+/ISH* +;
- Other advanced/unresectable or metastatic solid malignant tumor: determined by IHC, FISH, Next Generation Sequencing, or other analysis techniques as appropriate.
- ISH: FISH or DISH

8. Has adequate organ function within 7 days before the first treatment defined as:
- Platelet count greater than or equal to 100 000/mm^3
- Hemoglobin (Hb) greater than or equal to 9 g/dL
- Absolute neutrophil count (ANC) greater than or equal to 1500/mm^3
- Serum Creatinine less than or equal to 1.5 × ULN, or creatinine clearance greater than or equal to 60 mL/min (using Cockcroft-Gault formula).
- AST/ALT less than or equal to 3 × ULN (if liver metastases are present, less than or equal to 5 × ULN)
- Total bilirubin less than or equal to 1.5 × ULN
- Prothrombin time and activated partial thromboplastin time less than or equal 1.5 × ULN
- Cardiac troponin I less than 0.2 ng/mL

9. Has adequate treatment washout period before the first treatment, defined as:
- Major surgery greater than or equal to 4 weeks
- Radiation therapy greater than or equal to 4 weeks (if palliative stereotactic radiation therapy without abdominal, greater than or equal to 2 weeks)
- Autologous transplantation greater than or equal to 3 months
- Hormonal therapy greater than or equal to 2 weeks
- Chemotherapy or other target therapy (including antibody drug therapy) greater than or equal to 3 weeks (greater than or equal to 2 weeks for 5-fluorouracil-based agents, HER2-directed therapies greater than or equal to 4 weeks; folinate agents and/or weekly Paclitaxel; greater than or equal to 6 weeks for nitrosoureas or mitomycin C);
- Immunotherapy greater than or equal to 4 weeks
- CYP3A4 strong inhibitor greater than or equal to 3 elimination half-lives of the inhibitor
- Any investigational agents or treatments greater than or equal to 4 weeks
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cardiovascular dysfunction as defined by;
- Has a medical history of symptomatic CHF (NYHA classes II-IV) or serious cardiac arrhythmia requiring treatment;
- Has a medical history of myocardial infarction or unstable angina within 6 months before registration;
- Has a QTc prolongation to greater than 450 millisecond (ms) in males and greater than 470 ms in females based on 12-lead ECG in triplicate;

2. Cumulative anthracycline dose greater than 360 mg/m2 doxorubicin or equivalent;

3. Has a medical history of clinically significant lung diseases (e.g, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period, or requirement for supplemental oxygen;

4. Has an uncontrolled infection requiring i.v. of antibiotics, antivirals, or antifungals;

5. Known HIV infection, or active hepatitis B or C infection;

6. Is a lactating mother (Women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days before the first treatment;

7. Male and female subjects who are unwilling to use adequate contraceptive methods (e.g, concomitant use of a spermicidal agent, barrier contraceptive, or/and intrauterine contraceptive during the study and for at least 7 months after the last dose of GQ1001;

8. Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy;

9. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, grade less than or equal to 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the Investigator.

10. Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator;

11. Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product;

12. Grade greater than or equal to 2 peripheral neuropathy;

13. Active ulcer or incomplete healing of wound within 4 weeks prior to the first dose;

14. Patients who, as judged by investigators, are unable to complete the study plan due to objective conditions (including subject’s mental status, family relationship, social factor or geographical factor) or those who will be forced to withdraw the study halfway due to other factors, current therapy or abnormal laboratory examination.

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
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16551 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 30113 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 305545 0
Commercial sector/Industry
Name [1] 305545 0
Conjugate Light (Australia) Pty Ltd
Address [1] 305545 0
17 Bungowen Avenue, Thornleigh, NSW 2120
Country [1] 305545 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Conjugate Light (Australia) Pty Ltd
Address
17 Bungowen Avenue, Thornleigh, NSW, 2120
Country
Australia
Secondary sponsor category [1] 305950 0
Commercial sector/Industry
Name [1] 305950 0
GeneQuantum Healthcare (Suzhou) Co. Ltd.
Address [1] 305950 0
Unit 105A, Building A2, BioBay, No. 218, Xinghu Street
Suzhou Industrial Park, Suzhou, 215000
Country [1] 305950 0
China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305848 0
Bellberry Limited
Ethics committee address [1] 305848 0
123 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 305848 0
Australia
Date submitted for ethics approval [1] 305848 0
30/10/2019
Approval date [1] 305848 0
02/12/2019
Ethics approval number [1] 305848 0
2019-10-865

Summary
Brief summary
This purpose of this study is to determine a safe dose for GQ1001 in patients with HER-2 Positive Advanced Solid Tumors

Who is it for?
You may be eligible to join this study if you are aged between 18 and 65 years, and have pathologically documented solid tumor with HER2 expression

Study details
All participants in this study will receive the study drug (called GQ1001). There will be 5 groups of patients who each receive a different dose. The drug will be given once intravenously (through the vein) on Day 1 of a 21-day cycle. Participants will be monitored for reactions and treatment effectiveness, and provide blood and urine for analysis.

It is hoped that this research will improve the health outcomes of patients with HER2-positive advanced solid tumors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101806 0
Dr Charlotte Lemech
Address 101806 0
Scientia Clinical Research Ltd.
Levels 5 and 6, Bright Building, Corner High and Avoca Sts., Randwick, NSW 2031
Country 101806 0
Australia
Phone 101806 0
+61 293 825 807
Fax 101806 0
Email 101806 0
charlotte.lemech@scientiaclinicalresearch.com.au
Contact person for public queries
Name 101807 0
Ms Lisa Nelson
Address 101807 0
Scientia Clinical Research Ltd.
Levels 5 and 6, Bright Building, Corner High and Avoca Sts., Randwick, NSW 2031
Country 101807 0
Australia
Phone 101807 0
+61 293 825 811
Fax 101807 0
Email 101807 0
lisa.nelson@scientiaclinicalresearch.com.au
Contact person for scientific queries
Name 101808 0
Mr Paul Song
Address 101808 0
GeneQuantum Healthcare (Suzhou) Co. Ltd.
Unit 105A, Building A2, BioBay, No. 218, Xinghu Street
Suzhou Industrial Park, Suzhou, 215000
Country 101808 0
China
Phone 101808 0
+86 131 2076 2270
Fax 101808 0
Email 101808 0
paul@genequantum.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD data will stay at the clinical site with limited access to the authorized site staff only. The IPD data will not be shared with the Sponsor and any other third party.
What supporting documents are/will be available?
No other documents available
Summary results
No Results