NSCLC
Conditions
Brief summary
This study is a multicenter, open-label, single-arm phase II study to evaluate efficacy and safety of HA121-28 tablets in patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC).
Interventions
DRUGHA121-28 tablet
HA121-28 tablet, 450 mg, po, QD×21 days, every 4 weeks (28 days)
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate in this study and sign the informed consent form; 2. Aged 18 \ 75 years old (inclusive), male or female; 3. Patients with histologically or cytologically confirmed unresectable locally advanced or metastatic non-small cell lung cancer; 4. RET gene fusion, as demonstrated by Next-generation sequencing(NGS) method in central laboratory with College of American Pathologists(CAP) or Clinical Laboratory Improvement Amendments(CLIA) certification; 5. Progressive disease after at least one line of standard therapy (including patients with disease progression during or within 6 months of the end of adjuvant therapy); 6. At least one measurable lesion according to RECIST 1.1 (for lesions previously treated with radiation, the lesion can be included as a measurable lesion only if there is clear disease progression after radiotherapy); 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1; 8. Adequate organ function, laboratory tests meeting the following criteria: * Neutrophil count (ANC) ≥ 1.5 × 10\^9/L (no G-CSF for WBC-elevating therapy within 2 weeks prior to the laboratory test); * Platelet count (PLT) ≥ 75 × 10\^9/L (no platelet transfusion or other drugs to promote platelet production within 2 weeks prior to the laboratory test); * Hemoglobin (Hb) ≥ 90 g/L; (not receiving red blood cell transfusion or erythropoiesis-stimulating drugs within 2 weeks prior to the laboratory test); * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases); * Serum total bilirubin (TBIL) ≤ 1.5 × ULN; * Serum creatinine ≤ 1.5 × ULN; * Albumin ≥ 30 g/L; 9. Male and female patients of childbearing age agree to take effective contraceptive measures during treatment and within 6 months after the completion of treatment.
Exclusion criteria
1. Had a documented oncogenic driver gene alteration other than RET in NSCLC, ie, activating EGFR, BRAF, or KRAS mutation, MET exon 14 skipping mutation or high-level amplification, and ALK, ROS1, or NTRK1/2/3 gene fusions; 2. Prior treatment with selective RET inhibitors (including investigational selective RET inhibitors, such as LOXO-292, BLU-667, RXDX-105, etc.); 3. Patients who previously received any anti-tumor therapy (including but not limited to chemotherapy, radiotherapy and targeted therapy, etc.) within 4 weeks before the first use of the study drug; traditional Chinese medicine or Chinese patent medicine with anti-tumor indications within 2 weeks; local palliative radiotherapy for the relief of bone metastasis pain within 2 weeks; 4. Abnormal coagulation function (INR \> 1.5 or APTT \> 1.5 × ULN); patients with bleeding tendency (such as active peptic ulcer) or receiving thrombolytic or anticoagulant therapy; 5. Urine routine showed urine protein ≥ + + and 24 h urine protein \> 1.0 g; 6. Patients who have undergone major surgical procedures within 4 weeks before the first dose or are expected to undergo major surgery during the study; 7. Patients with central nervous system (CNS) metastases who present with progressive neurological symptoms or require an increase in corticosteroid dose to control their CNS disease. If a patient requires treatment with corticosteroids for CNS disease, the dose must be stable for two weeks prior to the first dose; 8. Presence of poorly controlled pericardial, pleural, or peritoneal effusion; 9. Interstitial pneumonia requiring steroid therapy, drug-induced pneumonitis, radiation pneumonitis (except for stable radiation pneumonitis); 10. Significant cardiovascular disease, such as heart failure greater than New York Heart Association (NYHA) Class 2, unstable angina, serious arrhythmia, myocardial infarction or stroke within 6 months prior to the first dose, poorly controlled hypertension (defined as systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg on multiple measurements while on medication); 11. Patients who met any of the following criteria will be excluded: * QT interval (QTcF) value ≥ 470 ms for females and ≥ 450 ms for males; or congenital long QT syndrome, taking drugs known to prolong QT interval, family history of long QT syndrome; * Resting ECG showed any clinically significant abnormalities in rhythm, conduction, or morphology that required clinical intervention; * Cardiac ejection fraction less than 50%; 12. Patients with active hepatitis B virus or hepatitis C virus infection: * HBsAg positive with HBV DNA higher than the upper limit of normal range of the study site; * HCV antibody positive with HCV RNA higher than upper limit of normal range of the site; 13. Human immunodeficiency virus infected (HIV positive); 14. Inability or severe dysphagia; 15. Patients who have suffered from or are complicated with any other malignant tumor within 5 years (except radically resected skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate cancer, in situ cervical cancer or other carcinoma in situ); 16. Presence of any severe and/or uncontrolled disease that may affect the drug evaluation in the judgment of the investigator, including but not limited to: life-threatening autoimmune system diseases; drug abuse; severe nervous system diseases (such as epilepsy, dementia, etc.); history of severe mental disorders; severe infection, etc.; 17. Pregnant or lactating women; 18. Other conditions that, in the opinion of the investigator, make participation in the study unsuitable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 12 months | The percentage of patients who achieve a complete response (CR) or partial response (PR) evaluated by Independent Review Committee (IRC) according to RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 12 months | Time from date of the first dose to date of recorded disease progression or death, whichever occurs first. |
| PFS | Up to approximately 12 months | Evaluated by investigator. |
| Overall survival (OS) | Up to approximately 24 months | Time from date of the first dose to date of death from any cause. |
| Disease Control Rate (DCR) | Up to approximately 12 months | The percentage of patients who achieve a CR, PR or stable disease (SD) evaluated by IRC. |
| ORR | Up to approximately 12 months | The percentage of patients who achieve a CR or PR evaluated by investigator according to RECIST 1.1. |
| Duration of Response (DOR) | Up to approximately 12 months | Time from first documented response (CR or PR, whichever occurs first, evaluated by IRC) to date of disease progression or death due to any cause, whichever occurs first. |
| DOR | Up to approximately 12 months | Evaluated by investigator. |
| Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs). | Up to 28 days after the last administration of HA121-28 | The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0. |
| DCR | Up to approximately 12 months | Evaluated by investigator. |
Countries
China
Contacts
Primary ContactRuihua Xu, Ph.D
Outcome results
None listed