HER2 Expressing or Mutated Advanced Malignant Solid Tumors
Conditions
Brief summary
This is an open-label, phase I study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of GQ1005 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects.
Interventions
DRUGGQ1005
an antibody drug conjugate
Sponsors
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The general inclusion criteria for dose escalation in Part 1 and dose expansion in Part 2 are as follows: 1. Voluntary agreement to provide written informed consent； 2. Aged 18 years or older, both male and female. 3. The expected survival time is more than 3 months. 4. ECOG performance status Score 0 or 1. 5. LVEF ≥ 50% by ECHO or MUGA scan within 28 days prior to the first dose of study drug. 6. Histologically or cytologically confirmed malignancy with at least 1 measurable lesion as assessed by RECIST v1.1. 7. Good organ function, confirmed by the following laboratory test results at Screening and within 7 days prior to the first dose of study drug: Platelet count ≥ 100,000/mm3; hemoglobin ≥ 9g/dL; ANC ≥ 1500/mm3; Serum CREA ≤ 1.5 × ULN, or estimated CREA clearance ≥ 60 mL/min (Cockcroft-Gault equation); ALT and AST ≤ 3 × ULN (≤ 5 x ULN if liver metastases are present); Total bilirubin ≤ 1.5 x ULN for subjects with Gilbert's syndrome or ≤ 2 x ULN for subjects with liver metastases at baseline; Prothrombin time and activated partial thromboplastin time ≤ 1.5 × ULN; 8. Adequate washout period prior to the first treatment, defined as follows: Major surgery ≥ 4 weeks; radiotherapy ≥ 4 weeks (≥ 2 weeks if the radiotherapy is palliative stereotactic radiotherapy without abdominal involvement); seed-radioactive therapy ≥ 3 months; Nuclein therapy ≥ 3 months; autotransplantation ≥ 3 months; Hormone therapy ≥ 2 weeks or as per investigator's judgment (breast cancer subjects) Chemotherapy or targeted therapy (including antibody drug therapy) ≥ 2 weeks (5-FU-based drugs, folinic acid preparations and/or weekly paclitaxel therapy); * 2 weeks (or 5 half-lives, whichever is longer) (tyrosine kinase inhibitor); * 4 weeks (HER2-targeted biological therapy); * 6 weeks (nitrosourea or mitomycin C); * 3 weeks (any other chemotherapy/targeted therapy); * 2 weeks (Chinese patent medicine with clear antitumor indication) antitumor immunotherapy ≥ 4 weeks; Any investigational drug or treatment ≥ 4 weeks; Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4) ≥ 1 week; Organic Anion Transport Polypeptide (OATP) Inhibitors ≥ 1 week; Inclusion criteria for the dose escalation phase of Part 1 only: 9. Failure of standard treatment, or intolerance, or absence of standard treatment, confirmed by pathology, HER2 expression (including IHC1+, IHC2+, IHC3+ and/or ISH\*+) or subjects with advanced/unresectable or metastatic solid tumors with HER2 exon 19 or 20 mutations (non-small cell lung cancer only). If only ISH\*, NGS reports are available, contact the Medical Monitor. Inclusion criteria for part 2a only: 10. Failure of standard treatment, intolerance, or absence of standard treatment, confirmed by pathology, HER2 overexpression (IHC 3+ or IHC 2+ and ISH\* +) Advanced/unresectable or metastatic breast cancer. Inclusion criteria for part 2b only: 11. Advanced breast cancer with low HER2 expression, unresectable, or metastatic breast cancer that has failed standard treatment, or is not tolerated, or has no standard treatment, is confirmed by pathology. (IHC 2+ and ISH\*- or ISH unknown, or IHC 1+). Inclusion criteria for part 2c only: 12. Non-small cell lung cancer with a HER2 exon 19 or 20 mutation that has failed, or is not tolerated, or is confirmed by a documented pathology without standard treatment. Inclusion criteria for part 2d only: 13. Advanced/unresectable or metastatic solid tumors with HER2 expression that have failed standard therapy, are not tolerated, or are without standard therapy, and are confirmed by pathology, with HER2 overexpression preferred. (IHC 3+ or IHC 2+ or ISH\* +) Adenocarcinoma of gastric and gastroesophageal junction; Other preferred tumor types include HER2 overexpression. (IHC 3+ or IHC 2+ or ISH\* +) Urothelial cancer, biliary tract cancer, endometrial cancer; Breast cancer and non-small cell lung cancer are excluded. * ISH+: FISH or two-color in situ hybridization (DISH).
Exclusion criteria
Subjects must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events (AEs) | Up to 2 years | Incidence and severity of Treatment-emergent adverse events, treatment-related adverse events and serious adverse events, according to NCI-CTCAE Version 5.0 (The number of participants who had treatment-related side effects in population who had received one therapy at least). |
| Dose Limiting Toxicities (DLTs) | From first dose to the end of Cycle 1, 21 days | 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. |
| Maximal Tolerance Dose (MTD) or recommended phase II dose (RP2D) | 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 | The SRC will also determine the MTD/RP2D based on the totality of data for all tested dose levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Up to 2 years | The objective response rate will be analyzed according to the RECIST 1.1 standard tumor evaluation |
| Duration of Response (DoR) | Up to 2 years | DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death |
| Disease control rate (DCR) | Up to 2 years | DCR is defined as the rate of the sum of CR, PR and SD according to the RECIST 1.1 standard tumor evaluation. |
| Maximum concentration (Cmax) of GQ1005 | Up to2 years | The pharmacokinetics(PK) profile of GQ1005 |
| Progression-free survival (PFS) | Up to 2 years | Progression free survival (PFS) refers to the time from the date of first administration to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard |
| Overall Survival (OS) | Up to 2 years | Overall survival (OS) refers to the time from the date of first administration to (for any reason) death. The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard |
| Immunogenicity (anti-drug antibody ADA) | Up to 2 years | Percentage of subjects producing detectable anti-drug antibodies (ADA) |
| Time-to-response (TTR) | Up to 2 years | To preliminarily evaluate TTR in patients with advanced solid tumors |
| Time of peak plasma concentration (Tmax) | Up to2 years | The pharmacokinetics(PK) profile of GQ1005 |
| Area under the plasma concentration time curve (AUC) of GQ1005 | Up to 2 years | The pharmacokinetics(PK) profile of GQ1005 |
Countries
China
Contacts
Primary ContactYan Shi
Outcome results
None listed