Study of HA121-28 in Patients With Non-Small Cell Lung Cancer
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HA121-28 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
HA121-28 tablet, 450 mg, po, QD×21 days, every 4 weeks (28 days)
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- ORR [Up to approximately 12 months]
The percentage of patients who achieve a CR or PR evaluated by investigator according to RECIST 1.1.
- 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.
- DCR [Up to approximately 12 months]
Evaluated by investigator.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Voluntarily participate in this study and sign the informed consent form;
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Aged 18 ~ 75 years old (inclusive), male or female;
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Patients with histologically or cytologically confirmed unresectable locally advanced or metastatic non-small cell lung cancer;
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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;
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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);
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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);
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1;
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Adequate organ function, laboratory tests meeting the following criteria:
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Neutrophil count (ANC) ≥ 1.5 × 10^9/L (no G-CSF for WBC-elevating therapy within 2 weeks prior to the laboratory test);
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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);
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Hemoglobin (Hb) ≥ 90 g/L; (not receiving red blood cell transfusion or erythropoiesis-stimulating drugs within 2 weeks prior to the laboratory test);
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases);
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Serum total bilirubin (TBIL) ≤ 1.5 × ULN;
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Serum creatinine ≤ 1.5 × ULN;
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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:
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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;
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Prior treatment with selective RET inhibitors (including investigational selective RET inhibitors, such as LOXO-292, BLU-667, RXDX-105, etc.);
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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;
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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;
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Urine routine showed urine protein ≥ + + and 24 h urine protein > 1.0 g;
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Patients who have undergone major surgical procedures within 4 weeks before the first dose or are expected to undergo major surgery during the study;
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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;
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Presence of poorly controlled pericardial, pleural, or peritoneal effusion;
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Interstitial pneumonia requiring steroid therapy, drug-induced pneumonitis, radiation pneumonitis (except for stable radiation pneumonitis);
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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);
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Patients who met any of the following criteria will be excluded:
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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;
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Resting ECG showed any clinically significant abnormalities in rhythm, conduction, or morphology that required clinical intervention;
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Cardiac ejection fraction less than 50%;
- Patients with active hepatitis B virus or hepatitis C virus infection:
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HBsAg positive with HBV DNA higher than the upper limit of normal range of the study site;
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HCV antibody positive with HCV RNA higher than upper limit of normal range of the site;
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Human immunodeficiency virus infected (HIV positive);
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Inability or severe dysphagia;
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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);
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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.;
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Pregnant or lactating women;
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Other conditions that, in the opinion of the investigator, make participation in the study unsuitable.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Centre | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HA122-CSP-004