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Trial registered on ANZCTR


Registration number
ACTRN12622000513718
Ethics application status
Approved
Date submitted
23/02/2022
Date registered
31/03/2022
Date last updated
23/09/2022
Date data sharing statement initially provided
31/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-In-Human, Dose Escalation and Expansion Study of GQ1007 Alone and in Combination with Envafolimab in Subjects with HER2-expressing Advanced Solid Tumors
Scientific title
A Phase I, First-In-Human, Multicenter, Open-Label, Dose Escalation and Expansion Study of GQ1007 Alone and in Combination with Envafolimab in Subjects with HER2-expressing Advanced Solid Tumors
Secondary ID [1] 306175 0
GQ1007-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 324882 0
Condition category
Condition code
Cancer 322319 322319 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is first-in-human study including dose escalation and expansion of GQ1007-101 in subjects with human epidermal growth factor receptor 2 (HER2)-expressing advanced solid tumors.
GQ1007 is a HER2-targeting antibody-immune agonist conjugate (AIAC) which will be administered subcutaneously (SC) every two weeks as monotherapy or in combination with the checkpoint inhibitor envafolimab (400mg) administered SC every 4 weeks.
The study has 4 parts:
1. Part1 (Dose escalation for GQ1007 Monotherapy)
Up to five dose levels (0.3, 1.0, 2.0, 4.0, 6.0 mg/kg administered SC every two weeks) may be evaluated. Dose escalation will be guided by Bayesian Optimal Interval Design (BOIN) principles. Up to 30 participants are planned and not all the participants will receive each dose level.
2. Part 2 (Dose expansion for GQ1007 Monotherapy) to evaluate the safety and efficacy at the maximum tolerated dose (MTD)/ Dose recommended for dose expansion (DRDE) in subjects with selected HER2-expressing advanced solid tumors. Part 2 will have 3 cohorts and subject's tumor type will determine the subject's cohort in Part 2.
3. Part 3 (Dose escalation for GQ1007 + Envafolimab combination Therapy)
Up to 6 GQ1007 dose levels ( 0.15, 0.3, 1.0, 2.0, 4.0, 6.0 mg/kg SC every two weeks) may be evaluated. Dose escalation will be guided by BOIN principles. Up to 30 participants are planned and not all the participants will receive each dose level.
4. Part 4 (Dose expansion for GQ1007 +Envafolimab combination therapy) will evaluate the safety and efficacy of GQ1007 at the MTD/DRDE in combination with envafolimab 400 mg every 4 weeks in subjects with selected HER2-expressing advanced solid tumors.
GQ1007 and envafolimab administration will be performed by study site staff and documented in source documents and electronic case record forms (eCRF).
Part 1 and Part 3 will be separated from Part 2 and 4 by a month.
GQ1007 is supplied in single-dose glass vials, each containing 1 ml of 40 mg/ml liquid concentrate.
Envafolimab is supplied in 300mg/1.5 ml vials.
In Parts 1 and 2 (GQ1007 monotherapy), subjects will receive GQ1007 SC every two weeks on Day 1 each 2-week treatment cycle. In Parts 3 and 4, subjects will receive GQ1007 SC on day 1 of each 2-week treatment cycle and SC envafolimab 400 mg every 4 weeks (every other 2-week treatment cycle [cycle 1 Day 1, cycle 3 Day 1, cycle 5 Day 1]). For combination therapy, GQ1007 will be administered first and there will be a 30-40 minutes break between GQ1007 and envafolimab injections.
The GQ1007 dose level for individual subjects in Parts 1 and 3 (dose escalation) will vary depending on the dose level enrolling subjects at the time of study entry. The GQ1007 dose level in Parts 2 and 4 will be the MTD /DRDE determined in Parts 1 and 3, respectively. The envafolimab dose will be 400 mg every 4 weeks in both Parts 3 and 4.
If multiple study parts are open (enrolling) and a participants qualifies for multiple study parts, then the participant's assignment to a study part will be based on discussion between investigator and sponsor.
As each dose level for monotherapy and/or combination therapy is cleared (i.e. dose escalation has advanced beyond that dose level), participants receiving treatment at lower dose levels based on cohort-assigned dose level may be escalated to a higher cleared dose level per investigator discretion and after discussion with and approval from sponsor.
Participants on monotherapy will stay on monotherapy and subjects on combination therapy will stay on combination therapy. The treatment period in each part of the study includes up to 52 treatment cycles of two weeks per treatment cycle hence each each participant will receive the treatment for up to 2 years.
A safety review committee (SRC) consisting of the investigators and the sponsor's designated representatives will monitor safety throughout the study and make dose escalation decisions (including any decisions to explore intermediate, higher, or lower doses and/or alternative dosing schedules).
Intervention code [1] 322588 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330091 0
For Part 1and 3 (Dose escalation)
To determine the maximum tolerated dose (MTD) or the dose recommended for dose expansion (DRDE) as a composite outcome by evaluating the Dose-limiting toxicity (DLT) rate (a DLT is any toxicity of Grade 3 or higher occurring during the DLT observation period).
A DLT could be Grade 4 neutropenia, anemia, or leukopenia, Grade 4 thrombocytopenia, febrile neutropenia, Grade 3 or higher bilirubin increased, Grade 2 or higher myocarditis, Grade 2 or higher myelitis, encephalitis, myasthenia gravis, Grade 2 or higher uveitis or blurred vision.
Timepoint [1] 330091 0
Day 1 to Day 28 (the first two 2-week treatment cycle) after the first dose of study treatment.
Primary outcome [2] 330092 0
For Part 2 and 4 (Dose expansion)
To evaluate the efficacy of GQ1007 measured by Objective response rate (ORR) as a composite outcome, defined as the proportion of the subjects with a best overall response of complete response (CR) or partial response (PR) per investigator using Response evaluation criteria in Solid Tumor version 1.1 (Recist 1.1)
Timepoint [2] 330092 0
The tumor assessments will be performed every 6 weeks (Q6W) (plus or minus 7 days) (screening and then approximately 6, 12, 18, and 24 weeks after Cycle 1 Day 1) for the first 24 weeks and then every 12 weeks (Q12W) (plus or minus 7 days) thereafter until disease progression without regard for dose delays or interruptions.
Primary outcome [3] 330093 0
To evaluate the Safety and tolerability of GQ1007, which will be measured by a composite of :
1. Incidence and severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [NCI CTCAE v5.0]) of treatment-emergent AEs (TEAEs), serious adverse events (SAEs), immune-related adverse events (irAEs), and adverse events (AEs) leading to discontinuation from study treatment
2. Results from clinical laboratory test from blood samples
3. Cardiac enzymes (troponin I) assessed by blood test, Left Ventricular Ejaculation Fraction (LVEF) assessed by echocardiogram
3. Electrocardiograms
4. Vital signs-heart rate by pulse oximeter, blood pressure by sphygmomanometer
5. Eastern Cooperative Oncology Group (ECOG) performance status,
6. Physical examination findings
Timepoint [3] 330093 0
1. AE- Daily from first treatment dose until 30 days after the last treatment dose
2. Clinical laboratory, Cardiac enzyme , LVEF and ECG- At screening, Day 1 and Day 8 of cycle 1, 2 and 3, Day 1 of cycle 4-52, End of treatment visit (within 5 days after the last treatment dose), safety follow up visit (30 days after the last dose)
3. ECOG-at Screening, Day 1 of cycle 1-52, end of treatment visit (within 5 days after the last treatment dose) and safety follow up visit (30 days after the last dose)
4. Vital signs and physical examinations -at screening, Day 1, Day 5, and Day 8 of cycle 1, 2, and 3, Day 1 and Day 8 of cycle 4-7, Day 1 of cycle 8-52, end of treatment visit (within 5 days after the last treatment dose), and safety follow up visit (30 days after the last dose)
Secondary outcome [1] 404855 0
For Part 1 and 3,
To evaluate the efficacy of GQ1007, which will be measured by a composite of efficacy parameters: Objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression free survival (PFS) per investigator using RECIST 1.1 and overall survival
Timepoint [1] 404855 0
The tumor assessments will be performed every 6 weeks (Q6W) (plus or minus 7 days) (screening and then approximately 6, 12, 18, and 24 weeks after Cycle 1 Day 1) for the first 24 weeks and then every 12 weeks (Q12W) (plus or minus 7 days) thereafter until disease progression without regard for dose delays or interruptions.
Secondary outcome [2] 404856 0
For Part 2 and 4,
To evaluate the efficacy of GQ1007, which will be measured by a composite of efficacy parameters: DoR, DCR, and PFS per investigator using RECIST 1.1 and OS
Timepoint [2] 404856 0
The tumor assessments will be performed every 6 weeks (Q6W) (plus or minus 7 days) (screening and then approximately 6, 12, 18, and 24 weeks after Cycle 1 Day 1) for the first 24 weeks and then every 12 weeks (Q12W) (plus or minus 7 days) thereafter until disease progression without regard for dose delays or interruptions.
Secondary outcome [3] 404857 0
Serum PK parameters (like AUC, Cmax, Tmax, T1/2, volume of distribution and clearance) of GQ 1007 estimated using standard noncompartmental analysis (NCA) methods or other applicable analysis methods. For these assessment blood samples will be taken at different time point in all the four parts of study.
Timepoint [3] 404857 0
Blood will be collected at
For cycles 1 and 3:
Day 1 (predose, which is within 60 minutes before dosing, 2.5 hrs and 6 hrs after dosing), Day 2 (24 hrs after the dose), Day 3 (48 hours after the dose), Day 5 (96 hrs after the dose), Day 8 (168 hrs after the dose) and Day 11 (240 hrs after the dose)

For cycle 2:
Day 1 (predose and 2 hrs after the dose), Day 2 (24 hrs after the dose), Day 5 (96 hrs after the dose), and Day 8 (168 hrs after the dose)

For cycles 4-7:
Day 1 (predose, within 60 minutes of before the dose), and Day 2 (24 hrs after the dose)
Secondary outcome [4] 404902 0
To assess the immunogenicity of GQ1007 as monotherapy (Part 1 and 2)
Timepoint [4] 404902 0
Blood will be collected at Day 1 and day 8 of cycles 1-7, Day 1 of cycles 8-52, and end of treatment visit (within 5 days of last treatment dose)
Secondary outcome [5] 406895 0
To assess the immunogenicity of GQ1007 in combination with envafolimab by measuring the anti-drug antibodies (ADA) against GQ1007 (Part 3 and 4)
Timepoint [5] 406895 0
Blood will be collected at Day 1 and day 8 of cycles 1-7, Day 1 of cycles 8-52, and end of treatment visit (within 5 days of last treatment dose)

Eligibility
Key inclusion criteria
1. Male and female subjects more than or equal to 18 years of age with a life expectancy of more than 3 months.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Left ventricular ejection fraction (LVEF) more than or equal to 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before the first dose of study treatment.
4. Agrees to submit fresh tumor biopsy samples for biomarkers if any studied tumor is accessible.
5. Histologically or cytologically confirmed malignancy diagnosis and at least 1 measurable pathologically documented advanced/unresectable or metastatic solid tumor as assessed by RECIST 1.1.
6. Documented progressive disease, refractory to/intolerant of standard therapy, or there is no standard therapy.
7. Adequate organ function confirmed at screening and within 7 days before the first dose of study treatment as evidenced by platelet count (more than or equal to 100,000/mm3), hemoglobin (more than or equal to 8g/dl), Absolute neutrophil count (more than or equal to 1500/mm3), Serum creatinine (less than or equal to 1.5 × upper limit of normal[ULN], or estimated creatinine clearance more than or equal to 60 mL/min (Cockcroft-Gault formula), alanine transaminase and aspartate transaminase less than or equal to 2.5 × ULN (less than or equal to 5 × ULN if liver metastases are present), total bilirubin (less than or equal to 1.5 × ULN or less than or equal to 2 × ULN for subjects with Gilbert’s Syndrome), Prothrombin time and activated partial thromboplastin time (less than or equal to 1.5 × ULN).
8. Adequate washout period before the first treatment
-For any major surgery, radiation therapy, immunotherapy, and any investigational agents or treatments- more than or equal to 4 weeks,
-For autologous transplants - more than or equal to 3 months,
-For hormonal therapy - more than or equal to 2 weeks,
-For chemotherapy or targeted therapy- more than or equal to 2 weeks (for 5-flourouracil based agents, folinate agents, and/or weekly paclitaxel, tyrosine kinase inhibitors); more than or equal to 4 weeks for HER2-directed biologic therapies; more than or equal to 6 weeks for nitrosoureas or mitomycin C; more than or equal to 3 weeks for any other chemotherapy/targeted therapy.
Additional inclusion criteria for Part 1 and Part 3
9. Has the protocol specified malignancies such as breast cancer, gastric cancer, gastroesophageal junction cancer, urothelial cancer, salivary gland carcinoma, gallbladder carcinoma, cholangiocarcinoma, or non-small cell lung cancer.
Additional inclusion criteria for Part 2 and Part 4
10. Agrees to provide a HER2 test report from tumor biopsy performed within the past 6 months or an archived tumor sample collected within the past 6 months, and if neither is available, a fresh tumor biopsy to confirm HER2 status if any studied tumor is accessible.
Additional inclusion criteria for Part 2a
11. Has breast cancer with HER2 overexpression (immunohistochemistry [IHC] 3+ or [IHC 2+ and in situ hybridization]).
Additional inclusion criteria for Part 2b
12. Has breast cancer with HER2 low expression (immunohistochemistry [IHC] 2+ or ISH or IHC 1+). Subjects with HER2 low expression metastatic breast cancer who have exhausted treatments that can confer any clinically meaningful benefit are also eligible.
Additional inclusion criteria for Part 2c
13. Subject has either a solid malignant tumor with HER2 expression or HER2 mutation.
Additional Inclusion criteria for Part 4
14. Subjects either have HER2 overexpressing breast cancer and gastric or gastroesophageal junction adenocarcinoma: IHC 3+ or [IHC 2+ and in situ hybridization] or HER2 low expressing breast cancer: IHC 1+ or [IHC 2+ but ISH] or any other solid malignant tumor with HER2 HER2 expression or HER2 mutation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
2. Conditions requiring systemic treatment with either corticosteroids (more than 10 mg daily prednisone equivalent) within 7 days or taking any other immunosuppressive medication within 14 days prior to the first dose of study treatment.
3. Active autoimmune disease that required systemic treatment (disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years.
4. Prior organ or tissue allograft.
5. History of Grade 3 or higher toxicity related to prior T cell agonist or checkpoint inhibitor.
6. Poorly controlled diarrhea (e.g., watery stool, uncontrolled bowel movement with drugs, Grade more than or equal to 2 ).
7. Cardiovascular dysfunction or clinically significant cardiac disease.
8. Medical history of clinically significant lung disease.
9. Known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
10. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade 1 or less or baseline.
11. Cumulative anthracycline dose greater than 360 mg/m2 doxorubicin or equivalent.
12. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
13. Known human immunodeficiency virus (HIV) infection.
14. Active infection with hepatitis C or hepatitis B except that subjects with occult or prior hepatitis B infection may be included if Hepatitis B Virus's Deoxyribonucleic acid (DNA) is undetectable at the time of screening, and these subjects must be willing to monthly DNA testing and appropriate antiviral therapy as indicated.
15. A positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a certified nucleic acid test within the last 30 days before the first dose of study treatment.
16. Receipt of a live vaccine within 30 days prior to the first dose of study treatment.
17. Pregnant or lactating women
18. Unwilling to use adequate contraceptive methods during the study and for at least 7 months after the last dose of study tratments.
Additional exclusion criteria for Part 2 and Part 4
19. Subjects with multiple primary malignancies within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.

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
The study has 4 parts:
Part 1 (dose escalation for GQ1007 monotherapy) will comprise of five cohorts of different dose levels
Part2 (dose expansion for GQ1007 monotherapy)
Part3 (dose escalation for GQ1007 plus Envafolimab combination therapy) will comprise of up to 6 cohorts of different dose levels
Part 4 (dose expansion for GQ1007 plus Envafolimab combination therapy)
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Sponsor has decided to terminate the study early due to company's strategic change.
Date of first participant enrolment
Anticipated
25/05/2022
Actual
Date of last participant enrolment
Anticipated
9/10/2024
Actual
Date of last data collection
Anticipated
14/12/2026
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 21452 0
GenesisCare - St. Vincent's Sydney - Darlinghurst
Recruitment hospital [2] 21453 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 21454 0
Pindara Private Hospital - Benowa
Recruitment postcode(s) [1] 36353 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 36354 0
3168 - Clayton
Recruitment postcode(s) [3] 36355 0
4217 - Benowa

Funding & Sponsors
Funding source category [1] 310519 0
Commercial sector/Industry
Name [1] 310519 0
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Country [1] 310519 0
China
Primary sponsor type
Commercial sector/Industry
Name
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Address
Suite 105A, Building A2, No. 218 Xinghu Street,
Suzhou Industry Park, Jiangsu
215123, China
Country
China
Secondary sponsor category [1] 311709 0
None
Name [1] 311709 0
Address [1] 311709 0
Country [1] 311709 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310143 0
Bellberry HREC Limited
Ethics committee address [1] 310143 0
123, Glen Osmond Road Eastwood
SA 5063
Ethics committee country [1] 310143 0
Australia
Date submitted for ethics approval [1] 310143 0
22/12/2021
Approval date [1] 310143 0
21/02/2022
Ethics approval number [1] 310143 0

Summary
Brief summary
This is first in human study of a new treatment drug, GQ1007 for patients with cancer that involves HER2-expression in solid tumors. This study aims to determine the maximum safest dose of GQ1007 that may be administered to cancer patients, firstly as a single therapy and secondly in combination with envafolimab therapy.

Who is it for?
You may be eligible for this study if you are an adult aged 18 or older, you have been diagnosed with any breast cancer, gastric cancer, gastroesophageal junction cancer, urothelial cancer, salivary gland carcinoma, gallbladder carcinoma, cholangiocarcinoma, or non-small cell lung cancer that involves solid tumours with HER2 gene expression. Additional heart and cognitive function tests will be conducted to determine suitability for enrolment.

Study details
This study will be conducted as four substudies (Parts 1-4), participants who choose to enrol in this study will only participate in one of the substudies. Participants enrolled into Parts 1 and 2 will receive subcutaneous injections (into the skin rather than a vein or muscle) of GQ1007 every 2 weeks for 2 years. Participants enrolled into Parts 3 and 4 will also receive subcutaneous injections of GQ1007 every 2 weeks for 2 years, and will also receive subcutaneous injections of envafolimab every 4 weeks for 2 years. All participants will undergo additional tests (including blood tests, echocardiograms and imaging) to assess the effect of the treatment on their cancer, and to monitor for side effects. Study participation is anticipated to be a maximum of approximately 26 months (up to 28 days for screening, up to 2 years of study treatment, and a Safety follow up Visit at 30 (+7) days after the last dose of any study treatment) plus long-term follow-up for subsequent anticancer therapy and overall survival.

It is hoped this research will determine whether GQ1007 is safe and tolerable for patients with various cancer types. If GQ1007 is found to be safe, larger studies can then be conducted to determine the efficacy of this treatment which may then lead to improved quality of life and overall survival for future cancer patients.
A Safety Review Committee (SRC) consisting of the Investigators and the Sponsor’s designated representatives will monitor safety throughout the study and make dose escalation decisions (including any decisions to explore intermediate, higher, or lower doses and/or alternative dosing schedules).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116630 0
Dr Andrea Tazbirkova
Address 116630 0
Pindara Private Hospital,
Allchurch Ave, Benowa , QLD 4217.
Country 116630 0
Australia
Phone 116630 0
+61755889093
Fax 116630 0
+61755889781
Email 116630 0
[email protected]
Contact person for public queries
Name 116631 0
Yang Zhang
Address 116631 0
GeneQuantum, Building D, No. 398, Ruoshui Road, Suzhou Industrial Park, 215123, China
Country 116631 0
China
Phone 116631 0
+86 17751651299
Fax 116631 0
Email 116631 0
[email protected]
Contact person for scientific queries
Name 116632 0
Ke Chen
Address 116632 0
GeneQuantum, Building D, No. 398, Ruoshui Road, Suzhou Industrial Park, 215123, China,
Country 116632 0
China
Phone 116632 0
+86 13306139991
Fax 116632 0
Email 116632 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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