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

NCT05117658 | Unknown Phase 2

• 1 other identifier: HA122-CSP-004
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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).

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• ORR

  Up to approximately 12 months

• Progression-Free Survival (PFS)

  Up to approximately 12 months

• PFS

  Up to approximately 12 months

• Overall survival (OS)

  Up to approximately 24 months

• Disease Control Rate (DCR)

  Up to approximately 12 months

Study Arms (1)

HA121-28

EXPERIMENTAL

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

Interventions

HA121-28 tablet DRUG

HA121-28 tablet, 450 mg, po, QD×21 days, every 4 weeks (28 days)

HA121-28

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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:

Sponsors & Collaborators

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

Study Sites (1)

Sun Yat-sen University Cancer Centre

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (1)

• Ruan DY, Huang WW, Li Y, Zhao Y, Shi Y, Jia Y, Cang S, Zhang W, Shi J, Chen J, Lin J, Liu Y, Xu J, Ouyang W, Fang J, Zhuang W, Liu C, Bu Q, Li M, Meng X, Sun M, Yang N, Dong X, Pan Y, Li X, Qu X, Zhang T, Yuan X, Hu S, Guo W, Li Y, Li S, Liu D, Song F, Tan L, Yu Y, Yu X, Zang A, Sun C, Zhang Q, Zou K, Dan M, Xu RH, Zhao H. Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial. Signal Transduct Target Ther. 2025 Feb 28;10(1):62. doi: 10.1038/s41392-025-02155-5.

  PMID: 40016191 DERIVED

Central Study Contacts

Ruihua Xu, Ph.D

CONTACT

86-20-87343468; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 11, 2021
• Study Start: February 18, 2022
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: August 4, 2022

Record last verified: 2021-12

Locations

CN (1)