Study of HA121-28 in Patients With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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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).

Official Title
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A Single-Arm, Multi-Centre, Open-Label Phase II Study of HA121-28 in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer

Conditions
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NSCLC

Intervention / Treatment
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* Drug: HA121-28 tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily participate in this study and sign the informed consent form; Aged 18   75 years old (inclusive), male or female; Patients with histologically or cytologically confirmed unresectable locally advanced or metastatic non-small cell lung cancer; 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; 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); 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); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1; 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; 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: 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; Prior treatment with selective RET inhibitors (including investigational selective RET inhibitors, such as LOXO-292, BLU-667, RXDX-105, etc.); 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; 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; Urine routine showed urine protein ≥ + + and 24 h urine protein > 1.0 g; Patients who have undergone major surgical procedures within 4 weeks before the first dose or are expected to undergo major surgery during the study; 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; Presence of poorly controlled pericardial, pleural, or peritoneal effusion; Interstitial pneumonia requiring steroid therapy, drug-induced pneumonitis, radiation pneumonitis (except for stable radiation pneumonitis); 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); 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%; 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; Human immunodeficiency virus infected (HIV positive); Inability or severe dysphagia; 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); 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.; Pregnant or lactating women; Other conditions that, in the opinion of the investigator, make participation in the study unsuitable.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HA121-28<br>Patients will receive HA121-28 tablets at 450 mg once daily (QD) for 21 days on a 28-day treatment cycle. | Drug: HA121-28 tablet<br>* HA121-28 tablet, 450 mg, po, QD×21 days, every 4 weeks (28 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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. | Up to approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | The percentage of patients who achieve a CR or PR evaluated by investigator according to RECIST 1.1. | Up to approximately 12 months | 
| Progression-Free Survival (PFS) | Time from date of the first dose to date of recorded disease progression or death, whichever occurs first. | Up to approximately 12 months | 
| PFS | Evaluated by investigator. | Up to approximately 12 months | 
| Overall survival (OS) | Time from date of the first dose to date of death from any cause. | Up to approximately 24 months | 
| Disease Control Rate (DCR) | The percentage of patients who achieve a CR, PR or stable disease (SD) evaluated by IRC. | Up to approximately 12 months | 
| DCR | Evaluated by investigator. | Up to approximately 12 months | 
| Duration of Response (DOR) | 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. | Up to approximately 12 months | 
| DOR | Evaluated by investigator. | Up to approximately 12 months | 
| Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs). | The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0. | Up to 28 days after the last administration of HA121-28 |