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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04450732




Registration number
NCT04450732
Ethics application status
Date submitted
23/06/2020
Date registered
29/06/2020
Date last updated
5/12/2023

Titles & IDs
Public title
Safety of GQ1001 in Adult Patients With HER2-Positive Advanced Solid Tumors
Scientific title
A Phase 1, First-In-Human, Multicenter, Open-Label, Study of GQ1001, a HER2 Targeted Antibody-Drug Conjugate, Administered Intravenously, in Adult Patients With HER2-Positive Advanced Solid Tumors
Secondary ID [1] 0 0
GQ1001X2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-positive Breast Cancer 0 0
HER2-positive Biliary Tract Cancer 0 0
HER2-Positive Salivary Gland Carcinomas 0 0
HER2-Positive Advanced Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GQ1001

Experimental: Dose Escalation - GQ1001 will be administered intravenously every 21 days. Dose Escalation will be guided by a modified 3+3 design.

Experimental: Dose Expansion - GQ1001 at the Dose Recommended for Dose Expansion will be administered intravenously every 21 days. Dose expansion will further evaluate the MTD or DRDE in different types of malignant solid tumor in four cohorts.


Treatment: Drugs: GQ1001
anti-HER2 antibody drug conjugate
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting Toxicities (DLTs).
Timepoint [1] 0 0
End of Cycle 1 (21-day cycle)
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD) or Dose Recommended for Dose Expansion (DRDE)
Timepoint [2] 0 0
After each cohort completes the DLT observation period (Day 1 to Day 21 after the first dose of study treatment) or has a DLT or becomes not DLT-evaluable
Secondary outcome [1] 0 0
Incidence and Severity of Adverse Events (AEs)
Timepoint [1] 0 0
from baseline to 30 days after last dose
Secondary outcome [2] 0 0
Number of Participants with Abnormal Laboratory Values
Timepoint [2] 0 0
rom baseline through Cycle 8 (each cycle is 21 days) and up to 30 days from treatment discontinuationafter last dose
Secondary outcome [3] 0 0
Area Under the Plasma Concentration Versus Time Curve (AUC) of GQ1001
Timepoint [3] 0 0
through study completion, an average of 1 year
Secondary outcome [4] 0 0
Peak Plasma Concentration of GQ1001 (Cmax)
Timepoint [4] 0 0
through study completion, an average of 1 year
Secondary outcome [5] 0 0
Time at which the Cmax is Observed (Tmax)
Timepoint [5] 0 0
through study completion, an average of 1 year
Secondary outcome [6] 0 0
Half Life of GQ1001 (T1/2)
Timepoint [6] 0 0
through study completion, an average of 1 year
Secondary outcome [7] 0 0
Mean Residence Time of GQ1001 (MRT)
Timepoint [7] 0 0
through study completion, an average of 1 year
Secondary outcome [8] 0 0
Volume of Distribution of GQ1001 (Vd)
Timepoint [8] 0 0
through study completion, an average of 1 year
Secondary outcome [9] 0 0
Preliminary Efficacy of GQ1001 Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and CT of MRI scans
Timepoint [9] 0 0
through study completion, an average of 1 year
Secondary outcome [10] 0 0
Immunogenicity
Timepoint [10] 0 0
through study completion, an average of 1 year
Secondary outcome [11] 0 0
Preliminary Efficacy
Timepoint [11] 0 0
through study completion, an average of 1 year
Secondary outcome [12] 0 0
Preliminary Efficacy
Timepoint [12] 0 0
through study completion, an average of 1 year
Secondary outcome [13] 0 0
Preliminary Efficacy
Timepoint [13] 0 0
through study completion, an average of 1 year
Secondary outcome [14] 0 0
Preliminary Efficacy
Timepoint [14] 0 0
through study completion, an average of 1 year

Eligibility
Key inclusion criteria
1. Signed informed consent form and able to comply with the protocol;

2. Male and female subjects =18 years of age;

3. ECOG PS of 0 or 1, the estimated life expectancy = 3 months;

4. LVEF = 50% as determined by echocardiography (ECHO);

5. Patients must have pathologically documented advanced/unresectable or metastatic solid
tumor with HER2-positive (as defined below) that is relapsed or refractory to standard
therapy or for which there is no standard therapy and progressed. Patients must have a
least one measurable disease lesion. Tumor specimens to identify HER2 status should be
obtained within the past 6 months.

Definition of HER2-positive

- Advanced/unresectable or metastatic breast cancer: immunohistochemistry (IHC) 3+,
or IHC 2+ and in situ hybridization positive (ISH+)*;

- Advanced/unresectable or metastatic gastric or gastroesophageal junction
adenocarcinoma: IHC 3+, or IHC 2+ and ISH+*;

- Other HER2-positive advanced/unresectable or metastatic solid malignant tumor:
determined by IHC, ISH, Next Generation Sequencing, or other analysis techniques
as appropriate;

- ISH: fluorescence in situ hybridization (FISH) or dual in situ hybridization
(DISH); ISH positivity is defined as a ratio of = 2.0 for the number of HER2
gene copies to the number of signals for CEP17. ISH assay is not required
when IHC result is 3+. ISH assay should be performed to confirm HER2
positivity when IHC result is 2+.

6. Adequate organ function confirmed at screening and within 7 days before the first
treatment, as evidenced by:

Platelet count: = 100,000/mm3 ; Hemoglobin : = 9 g/dL; Absolute neutrophil count
(ANC): = 1500/mm3 ; Serum creatinine: = 1.5 × ULN (upper limit of normal), or
creatinine clearance = 60 mL/min (using Cockcroft Gault formula) ; Aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) : = 2.5 × ULN (= 5 × ULN if
liver metastases are present); Total bilirubin : = 1.5 × ULN (except for patients with
Gilbert's Syndrome); Prothrombin time and activated partial thromboplastin time: = 1.5
× ULN.

7. Adequate washout period before the first treatment as defined by:

Major surgery: = 4 weeks. Radiation therapy: = 4 weeks (= 2 weeks for palliative
stereotactic radiation therapy without abdominal). Autologous transplantation: = 3
months.

Hormonal therapy: = 2 weeks or per Investigator's discretion for breast cancer
patients.

Chemotherapy or targeted therapy (including antibody drug therapy): = 3 weeks (= 2
weeks for 5 flourouracil-based agents, folinate agents, and/or weekly paclitaxel; = 2
weeks (or 5 half-lives, whichever is shorter) for tyrosine kinase inhibitors; = 4
weeks for HER2-directed biologic therapies; = 6 weeks for nitrosoureas or mitomycin
C). Immunotherapy: = 4 weeks. Strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor: =
3 elimination half-lives . Any investigational agents or treatments: = 4 weeks.

8. Patients without a history of acquired immunodeficiency syndrome (AIDS)-defining
opportunistic infections or with a history of AIDS-defining opportunistic infections
and have not had an opportunistic infection within the past 12 months may be enrolled
per the discretion of the Investigator.
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. 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 chemotherapy or radiotherapy;

2. 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);

3. Cardiovascular dysfunction or clinically significant cardiac disease, including but
not limited to:

- Medical history of symptomatic chronic heart failure (New York Heart Association
(NYHA) classes II-IV) or serious cardiac arrhythmia requiring treatment;

- Medical history of myocardial infarction or unstable angina within 6 months of
the first treatment;

- Corrected QT interval by Fridericia (QTcF) prolongation of > 450 milliseconds
(ms) in males and > 470 ms in females;

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

5. Known hypersensitivity to either the drug substances or inactive ingredients in the
drug product;

6. Existing Grade = 2 peripheral neuropathy;

7. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other
than alopecia) not yet resolved to NCI CTCAE version 5.0, Grade = 1 or baseline.
Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the
Investigator;

8. Cumulative anthracycline dose > 360 mg/m2 doxorubicin or equivalent;

9. Uncontrolled infection requiring i.v. of antibiotics, antivirals or antifungals;

10. Active infection with hepatitis C (e.g., detectable antibodies to hepatitis C virus
[HCV]) or hepatitis B (e.g., hepatitis B surface antigen [HBsAg] positive) except
subjects with occult or prior hepatitis B infection (defined as positive total
hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus
(HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening, and these
subjects must be willing to undergo monthly DNA testing and appropriate antiviral
therapy as indicated;

11. Patients with a history or current evidence of any concomitant condition, therapy, or
laboratory abnormality that, in the opinion of the Investigator, might confound the
results of the trial, interfere with the patient's participation and compliance;

12. Women who are lactating or pregnant, as confirmed by pregnancy test within 7 days
before first treatment;

13. 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.

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
7/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2024
Actual
Sample size
Target
96
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Scientia Clinical Research Limited - Randwick
Recruitment hospital [2] 0 0
Cabrini Institute in Melbourne, Australia - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
China
State/province [2] 0 0
Anhui
Country [3] 0 0
China
State/province [3] 0 0
Beijing
Country [4] 0 0
China
State/province [4] 0 0
Guangdong
Country [5] 0 0
China
State/province [5] 0 0
Henan
Country [6] 0 0
China
State/province [6] 0 0
Hubei
Country [7] 0 0
China
State/province [7] 0 0
Hunan
Country [8] 0 0
China
State/province [8] 0 0
Liaoning
Country [9] 0 0
China
State/province [9] 0 0
Shandong
Country [10] 0 0
China
State/province [10] 0 0
Shanghai
Country [11] 0 0
China
State/province [11] 0 0
Sichuan
Country [12] 0 0
China
State/province [12] 0 0
Zhejiang

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase I Dose Finding Study for GQ1001 in Patients with HER2-Positive Advanced Solid Tumors
Trial website
https://clinicaltrials.gov/ct2/show/NCT04450732
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Yan Shi
Address 0 0
Country 0 0
Phone 0 0
0512-66526166
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04450732