Overview
The aim of this trial is to study the safety, pharmacokinetics and preliminary efficacy of the HER2-targeted antibody-drug conjugate GQ1001 in combination with pyrotinib in patients with HER2-positive metastatic breast cancer patients who had failed previous anti-HER2 treatment.
Eligibility
Inclusion Criteria:
- Ability to understand and the willingness to provide written informed consent.
- Men or women aged 18-75.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy greater than 3 months.
- Left ventricular ejection fraction (LVEF) ≥50%.
- Histopathological and/or cytological confirmed Her2-positive locally advanced or metastatic breast cancer (IHC3+, or IHC2+ and ISH+)
- Failure for at least 1 line of standard systemic treatment for metastatic disease.
Meet one of the following conditions:
- Recurrent within 12 months after completing or during neoadjuvant/ adjuvant therapy (the regimens contain trastuzumab or its biosimilar with pertuzumab or not).
- Received at least one treatment with trastuzumab or its biosimilar ±pertuzumab (monotherapy or in combination with other drugs) for recurrent or metastatic disease.
- Previous exposure to taxanes. 9. Having at least one measurable lesion according to RECIST 1.1 . 10. Having sufficient bone marrow, liver and kidney functions: white blood cell count≥ 3×109/L; Absolute neutrophil count ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days; Total bilirubin ≤ 1.5 x the upper limit of normal (ULN); AST and ALT ≤ 3.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases); Serum creatinine ≤1.5 x ULN; Coagulation function (prothrombin time and activated partial thromboplastin time ≤1.5 x ULN); 11. Adequate wash-out periods: Major surgery ≥4 weeks; radiotherapy ≥4 weeks; targeted therapy or chemotherapy≥4 weeks; endocrine therapy≥2 weeks; targeted therapy and endocrine therapy≥2 weeks; mAbs and immunotherapy ≥4 weeks; Any investigational agents≥4 weeks; potent CYP3A4 inhibitor≥3*t1/2 weeks.
- Female subjects must meet the following conditions: infertility or fertility and use high-efficiency contraceptive measures during the study and for 6 months following the last dose of the study drug infusion.
Exclusion Criteria:
- Have active brain parenchymal metastasis. Patients with clinically stable brain parenchymal metastases can be included, including asymptomatic brain metastases that have not received local treatment; or patients who have previously received central nervous system metastasis therapy (radiotherapy or surgery), if imaging confirms that stability has been maintained for at least 4 weeks, and have stopped symptomatic treatment (including hormones and mannitol, etc.) for more than 4 weeks CNS (central nervous system) metastasis with clinical symptoms;
- Have previously been treated with: another antibody-drug conjugate (ADC) consisting of DM1 or its derivative; previously received capecitabine (end of adjuvant therapy>1 year and not receive capecitabine after relapse were allowed); previously received pyrotinib (end of (neo)adjuvant therapy>6 months and no pyrotinib treatment after relapsed were allowed; received pyrotinib in metastatic settings and stopped for reasons other than disease progression and had disease progression after 6 months were allowed.
- Have other malignant tumors within 5 years before signing the informed consent form ( except for cured skin basal cell carcinoma and cervical carcinoma in situ).;
- The toxicity of previous anti-cancer therapy has not recovered to ≤1 as specified in CTCAE v5.0 (except for hair loss); chronic grade 2 toxicity might be determined per the investigator's judgment.
- History of allergic reaction to any component of GQ1001.
- Have a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia within 6 months.
- Have a corrected QT interval (QTc) prolongation to > 450 milliseconds (ms) in males and > 470 ms in females.
- Have a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis requiring steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- The cumulative dose of anthracyclines or equivalent>500 mg/m2.
- Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), and hepatitis C (HCV).
- Pregnancy or lactation.
- Male or female subjects unwilling to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for 7 months following the last dose of the study drug infusion.
- Other circumstances that are deemed not appropriate for the study.
- Inability to swallow, chronic diarrhea and intestinal obstruction, or other factors that affect drug administration and absorption.