A Phase 1, First-In-Human, Multicenter, Open-Label,Dose-Escalation and Extension Study of GQ1005 in Subjects With HER2-Expressing Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- GQ1005
- Conditions
- HER2 Expressing or Mutated Advanced Malignant Solid Tumors
- Sponsor
- GeneQuantum Healthcare (Suzhou) Co., Ltd.
- Enrollment
- 150
- Locations
- 19
- Primary Endpoint
- Dose Limiting Toxicities (DLTs)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The general inclusion criteria for dose escalation in Part 1 and dose expansion in Part 2 are as follows:
- •Voluntary agreement to provide written informed consent；
- •Aged 18 years or older, both male and female.
- •The expected survival time is more than 3 months.
- •ECOG performance status Score 0 or
- •LVEF ≥ 50% by ECHO or MUGA scan within 28 days prior to the first dose of study drug.
- •Histologically or cytologically confirmed malignancy with at least 1 measurable lesion as assessed by RECIST v1.
- •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;
- •Adequate washout period prior to the first treatment, defined as follows:
Exclusion Criteria
- •Subjects must not meet any of the following exclusion criteria to be enrolled in the study.
- •Clinically active brain metastases, defined as untreated and symptomatic, or requiring treatment with steroids or anticonvulsants to control associated symptoms. Subjects with treated asymptomatic brain metastases who do not require steroid therapy may be included in the study if they have recovered from the acute toxicity of radiation therapy.
- •Cardiovascular dysfunction or clinically significant cardiac conditions, including but not limited to:
- •Symptomatic CHF (New York Heart Association classes II to IV) or severe cardiac arrhythmia requiring treatment
- •History of myocardial infarction or troponin levels consistent with myocardial infarction (defined by the American College of Cardiology guidelines) within 6 months prior to the first dose, and unstable angina pectoris within 6 months prior to the first dose of study drug;
- •QTcF prolongation at Screening \>460 milliseconds (ms) (male) and \>470 ms (female) except for right bundle branch block.
- •Clinically significant acute and chronic lung disease. (e.g., interstitial pneumonia, pulmonary infection, pulmonary fibrosis, and severe radiation pneumonitis), or subjects with suspected pulmonary disease based on imaging at screening, or subjects requiring oxygen.
- •People with known hypersensitivity to recombinant humanized anti-HER2 monoclonal antibody-DXd conjugate drugs and their components or to humanized monoclonal antibody products.
- •Poorly controlled pleural, ascites, or pericardial effusions.
- •Toxicity that has not resolved from prior antineoplastic therapy, defined as toxicity (other than alopecia) that has not resolved to ≤ Grade 1 or baseline levels, is at the discretion of the investigator for the eligibility of subjects with chronic Grade 2 toxicities.
Arms & Interventions
Dose Escalation
GQ1005 will be administered intravenously every 21 days. Dose Escalation will be guided by Bayesian Optimal Interval (BOIN) Design. Multiple dose grouping
Intervention: GQ1005
Dose Expansion
GQ1005 at the recommended phase II dose (RP2D) will be administered intravenously every 21 days. Dose expansion will further evaluate the MTD or RP2D in different types of malignant solid tumor in four cohorts.
Intervention: GQ1005
Outcomes
Primary Outcomes
Dose Limiting Toxicities (DLTs)
Time Frame: 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.
Incidence and Severity of Adverse Events (AEs)
Time Frame: 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).
Maximal Tolerance Dose (MTD) or recommended phase II dose (RP2D)
Time Frame: 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 Outcomes
- Area under the plasma concentration time curve (AUC) of GQ1005(Up to 2 years)
- Overall response rate (ORR)(Up to 2 years)
- Maximum concentration (Cmax) of GQ1005(Up to2 years)
- Time-to-response (TTR)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Immunogenicity (anti-drug antibody ADA)(Up to 2 years)
- Time of peak plasma concentration (Tmax)(Up to2 years)
- Duration of Response (DoR)(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)