New hope for Hard-to-Treat cancers: A166 targets HER2 tumors

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Voluntarily sign informed consent form; 2. Age ≥ 18 years old, no gender limit; 3. Patients had a histologically confirmed incurable locally advanced or metastatic solid tumors; 4. Determined HER2-positive disease (detected by ISH or NGS) or HER2-expressing disease by evaluation or detection. Definition of HER2 expression in this study: Immunohistochemistry \[IHC\] ≥ 1＋; 5. Patients unable to benefit from the available standard treatment according to the judgment of the investigator; 6. White blood cell count (WBC) ≥ 4.0×109/L or ≥ lower limit of normal value; Neutrophil count (NEUT) ≥ 1.5×109/L; Platelet count (PLT) ≥ 100×109/L; Hemoglobin concentration ≥ 9.0 g/dL; 7. Total bilirubin (TBIL) ≤ 1.5×ULN. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN). For patients with liver metastases, ALT and AST ≤ 5 times ULN, and for patients with liver and/or bone metastases, alkaline phosphatase ≤ 5 times ULN; 8. Creatinine clearance rate ≥ 50 ml/min; 9. Patients had an Eastern Cooperative Oncology Group (ECOG)performance status of 0 or 1, the expected survival time is ≥ 3 months; 10. During the study period and within 7 months after the final administration of A166, patients with fertility (regardless of male and female) must receive effective medical contraceptive measures; 11. The patients must recover from all acute toxicities of the previous treatment (relieved to grade 1 or baseline), except for hair loss and vitiligo; Exclusion Criteria: 1. Severe or uncontrollable heart disease requiring treatment, or grade 3 or 4 congestive heart failure according to the New York Society of Cardiology (NYHA), or unstable angina pectoris that cannot be controlled by drugs, or history of myocardial infarction within 6 months prior to enrollment, or severe arrhythmia requiring medical treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia); 2. History of ≥ Grade 3 allergic reaction to trastuzumab; 3. Permanent with drawal of trastuzumab due to any previous toxicity; 4. Patients with brain metastases who have symptoms or who have received the radiotherapy or surgery within 3 months before the first administration; 5. Patients requiring oxygen therapy in daily activities; 6. Grade 2 or higher peripheral neuropathy; 7. Any chemotherapy, hormone therapy (except dexamethasone), radiotherapy, immunotherapy or biological therapy received within 4 weeks before the first administration; 8. Prior-treatment with other clinical research drugs within 4 weeks before the first administration; 9. Patients who have undergone major surgery within 4 weeks before the first administration; 10. Active hepatitis B (hepatitis B surface antigen positive and HBV-DNA higher than the upper limit of reference value) or hepatitis C (positive hepatitis C virus antibody and HCV-RNA higher than the upper limit of reference value); current or past alcoholics ; Liver cirrhosis; 11. Known active human immunodeficiency virus (HIV); 12. Systemic diseases that cannot be controlled, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, glaucoma, etc according to investigator's judgment; 13. Current pregnancy or lactation; 14. QTc interval\> 470 ms according to the baseline measurement:; 15. Left ventricular ejection fraction (LVEF) \<45% according to the echocardiogram (ECHO) or multi-gate circuit controlled acquisition (MUGA) ; 16. Previous cumulative doxorubicin accumulation \> 360 mg/m2 or its equivalent dose;