Neratinib Tablets Monotherapy for Advanced Solid Tumors With HER2 Mutations

A Single-arm, Open-label, Multicenter Phase II Clinical Study of Neratinib Tablets Monotherapy in the Treatment of Advanced Solid Tumors With HER2 Mutations

Evaluating the efficacy of Neratinib tablets monotherapy in treating advanced solid tumors with HER2 mutations.

This single-arm, open-label, multicenter Phase II clinical study is divided into three phases: screening, treatment, and follow-up. The screening phase occurs within 28 days prior to the first administration of the study drug. During the treatment phase, a 28-day cycle is used, and tumor efficacy is assessed according to the RECIST 1.1 criteria. Assessments are conducted at the end of the first cycle (±3 days), followed by imaging evaluations every 8 weeks until disease progression. During the treatment period, the investigator may increase the number of assessments based on clinical needs. The study drug will be administered continuously until intolerable adverse reactions occur, disease progression, withdrawal of informed consent, loss to follow-up, death, or study termination.

The follow-up phase includes safety and survival follow-up. Safety follow-up occurs within 28 days after the last administration of the study drug. Survival follow-up is conducted every 12 weeks to collect the survival status of the subjects until their death, loss to follow-up, withdrawal from the study, or study termination (whichever occurs first).

Inclusion Criteria:

• 1.Age is 18 years or older, and the patient can be male or female;
• 2.Histologically or cytologically confirmed advanced non-small cell lung cancer, cholangiocarcinoma, cervical cancer, and salivary gland cancer patients; those who have failed to respond to ≤2 lines of standard treatment (disease progression after treatment or intolerable toxic side effects of treatment), or have no standard treatment options, or are unable to receive standard treatment;
• 3.Previously underwent second-generation sequencing testing with evidence of HER2 mutation, otherwise, the patient must provide sufficient tissue samples for second-generation sequencing testing in the study's central laboratory, with tissue samples being the primary source; if tissue slices or samples that meet the requirements cannot be obtained, blood samples may be provided for testing.
• 4.According to the RECIST v1.1 criteria (see Appendix 1), there must be at least one measurable lesion; if the only lesion is one that has previously received local treatment (such as radiotherapy, ablation, interventional treatment, etc.), there must be clear radiological evidence of disease progression;
• 5.Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
• 6.Predicted survival is 3 months or more;
• 7.Bone marrow reserve must meet the following laboratory value criteria: Absolute neutrophil count (ANC) is ≥1.5 × 10^9/L; Platelet count (PLT) is ≥90 × 10^9/L; Hemoglobin (Hb) is ≥90 g/L; Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) are ≤2.5 × ULN (the upper limit of the normal range); if liver metastasis is present, it should be ≤5 × ULN; Total bilirubin (TBIL) is ≤1.5 × ULN; Blood urea/urea nitrogen (UREA/BUN) and Creatinine (Cr) are ≤1.5 × ULN; Coagulation function: International normalized ratio (INR) and Activated partial thromboplastin time (APTT) are ≤1.5 × ULN; Urine protein is less than 2+ (if baseline urine protein is ≥2+, a 24-hour urine protein quantification should be performed, and it is acceptable for inclusion if ≤1g);
• 8.Women of reproductive age should agree to use contraceptive measures (such as intrauterine devices, hormonal contraceptives, or condoms) during the study period and for 6 months after the study ends; they must have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must not be breastfeeding; men should agree to use contraceptive measures during the study period and for 6 months after the study ends;
• 9.The subject can understand the nature of this study, and the subject and/or legal representative voluntarily agrees to participate in this trial and signs the informed consent.

Exclusion Criteria:

• 1.Patients who have previously received treatment with any HER2-targeted tyrosine kinase inhibitors (such as lapatinib, pyrotinib, neratinib, etc.);
• 2.Those who do not meet the following requirements for the washout period from previous anti-tumor treatments before the first administration of the study drug: the washout time from the end of the last dose of previous anti-tumor treatment to the first administration of the study drug (calculated from the end of the last dose) is as follows: chemotherapy ≥3 weeks (oral fluorouracil ≥2 weeks; mitomycin C, nitrosoureas ≥6 weeks), small molecule targeted therapy ≥2 weeks, large molecule drugs (including immunotherapy) ≥4 weeks, radiotherapy ≥4 weeks (local palliative radiotherapy ≥2 weeks), Chinese medicine with anti-tumor indications ≥2 weeks, other anti-tumor treatments ≥4 weeks, investigational drugs or treatments that are not yet marketed ≥4 weeks;
• 3.Received major organ surgery (excluding biopsy) or had significant trauma within 4 weeks before the first administration of the study drug;
• 4.Spinal cord compression or brain metastasis, unless asymptomatic, stable, and has not required steroid treatment for at least 4 weeks before the start of the study treatment (before dosing);
• 5.A history of other malignant tumors within the past 5 years, excluding cured cancers such as cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;
• 6.Adverse reactions from previous anti-tumor treatments have not recovered to a grade of ≤1 according to CTCAE 5.0 (except for toxicities judged by the investigator to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, thyroid hypothyroidism stable with hormone replacement therapy);
• 7.The presence of uncontrollable third-space fluid accumulation (such as a large amount of pleural effusion, ascites, or pericardial effusion) that cannot be managed by drainage or other methods;
• 8.Patients with gastrointestinal diseases that may affect drug absorption (such as Crohn's disease, intestinal obstruction, active peptic ulcer disease, etc.);
• 9.Patients currently suffering from interstitial lung disease;
• 10.Patients with any cardiac disease, including: (1) unstable angina; (2) clinically significant arrhythmias requiring medication; (3) myocardial infarction; (4) heart failure of grade 3 or higher; (5) echocardiography: left ventricular ejection fraction (LVEF) ≤50%; (6) 12-lead electrocardiogram: QTcF: females >470 milliseconds, males >450 milliseconds; (7) any other cardiac disease judged by the investigator to be unsuitable for participating in this trial;
• 11.History of immunodeficiency, including HIV antibody test positive;
• 12.Active hepatitis B or C (HBV DNA, HCV RNA test results at screening are not within the normal range of the central laboratory);
• 13.According to the investigator's judgment, there are other serious accompanying diseases that endanger patient safety or affect the patient's ability to complete the study (such as uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg after taking antihypertensive drugs), diabetes (glycated hemoglobin >9.0%), autoimmune diseases, etc.);
• 14.The investigator deems the subject unsuitable for other reasons to participate in this study.