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

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

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).

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: HA121-28 tablet

• Study Type: Interventional
• Enrollment (Anticipated): 83
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ruihua Xu, Ph.D; Phone Number: 86-20-87343468; Email: xurh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Centre
      • Contact: Ruihua Xu, Ph.D; Phone Number: 86-20-87343468; Email: xurh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HA122-CSP-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No