Phase I Dose Finding Study in Patients with HER2-Positive Advanced Solid Tumors
A Phase I, 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
Conjugate Light (Australia) Pty Ltd
13 participants
Jun 25, 2020
Interventional
Conditions
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 18 years and older, 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.
Eligibility
Inclusion Criteria27
- Patients who are voluntary to participate in this clinical study, able to understand the study procedure, and have signed the informed consent form.
- Male or female subjects 18 years of age and older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening;
- Left ventricular ejection fraction (LVEF) greater than or equal to 50% by echocardiography
- 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
- +/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
- 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 2.5 × 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
- 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.
- Patients without a history of 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.
Exclusion Criteria16
- 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;
- Any hematologic malignancies, including leukemia (any form), lymphoma, and multiple myeloma;
- 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;
- 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;
- Known hypersensitivity to either the drug substances or inactive ingredients in the drug product;
- Grade greater than or equal to 2 peripheral neuropathy;(Note: for patients who relapsed or refractory to Kadcyla®, patients who have grade = 2 peripheral neuropathy may be eligible per the discretion of the Investigator after discussion with the Sponsor);
- 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;
- Cumulative anthracycline dose greater than 360 mg/m2 doxorubicin or equivalent;
- Uncontrolled infection requiring i.v. of antibiotics, antivirals or antifungals;
- Active infection of hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g. HCV RNA (qualitative) is detected);
- 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
- Women who are lactating or pregnant, as confirmed by pregnancy test within 7 days before first treatment;
- 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;
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Interventions
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.
Locations(1)
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ACTRN12620000592943