A Phase III, Open-Label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of SY-5007, a RET Inhibitor, in Patients With Locally Advanced or Metastatic RET Fusion-positive NSCLC.

Shouyao Holdings (Beijing) Co. LTD1 site in 1 country120 target enrollmentJune 20, 2023

ConditionsNon-Small Cell Lung Cancer

InterventionsSY-5007

DrugsSY-5007

Overview

Phase: Phase 3
Intervention: SY-5007
Conditions: Non-Small Cell Lung Cancer
Sponsor: Shouyao Holdings (Beijing) Co. LTD
Enrollment: 120
Locations: 1
Primary Endpoint: Assessment of ORR by independent review committee (IRC).
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase III, open-label, single-arm, multicenter study designed to evaluate the anti-tumor activity and safety of SY-5007 administered orally to participants with locally advanced or metastatic RET-positive NSCLC.

Detailed Description

This study will enroll patients with locally advanced or metastatic RET-positive NSCLC. SY-5007 will be administered orally 160 mg twice daily in 28-day cycle continuously until disease progression, death, unacceptable toxicity, withdrawal of consent, or protocol-specified parameters. This study is designed to evaluate the anti-tumor activity (over response rate \[ORR\], disease control rate \[DCR\], duration of response \[DOR\], progression free survival \[PFS\] and overall survival \[OS\]) and safety of SY-5007 in patients.

Registry

clinicaltrials.gov

Start Date

June 20, 2023

End Date

June 20, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shouyao Holdings (Beijing) Co. LTD

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female, at least 18 years old.
•Histologically or cytologically confirmed diagnosis of locally advanced (with a tumor lesion that cannot be eradicated by surgery or radiotherapy as assessed by the investigators) or metastatic NSCLC.
•No prior systemic antitumor therapy for locally advanced or metastatic NSCLC (Note: enrollment is permitted in the following 2 situations: 1) received only adjuvant therapy and the end of treatment was ≥ 6 months prior to the first dose; 2) received only radical radiotherapy and the end of treatment was ≥ 6 months prior to the first dose).
•The patient's tumor tissue or blood sample test result meets 1 of the following two criteria: a. Previous tumor tissue or blood samples are confirmed as RET fusion positive by local laboratory testing. b. If there is no previous RET fusion positive test report, a compliant tumor tissue or blood sample is required to be provided at the central laboratory, using a next-generation sequencing (NGS)-based assay to confirm RET fusion positive.
•Patients have at least one measurable lesion per RECIST version 1.
•(except for patients with measurable lesions in the brain only) (Note: a lesion that has been treated with radiotherapy or localized therapy is generally not considered a measurable lesion unless there is definitive progression of that lesion).
•Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1;
•Life expectancy of at least 3 months.
•Patients must have adequate organ function as defined in the below:
•Bone marrow function:

Exclusion Criteria

•Patients carried known major driver genetic alterations other than RET. e.g. EGFR, MET, ALK, ROS1, NTRK, BRAF V600, KRAS G12C, etc. (If a patient has a co-mutation, discuss with the investigators whether enrollment is possible).
•History of allergy to any components or excipients of SY-5007 tablets.
•Patients with malignancies other than NSCLC treated in this study (except: malignancies that are cured and have not recurred within 2 years prior to study entry; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of the cervix or breast).
•Patient has clinically symptomatic primary central nervous system (CNS) tumor, symptomatic CNS metastases, molluscum contagiosum, or untreated spinal cord compression; exclusion: patient has stable CNS disease (no evidence of progression as determined by imaging for at least 4 weeks prior to the first dose and all neurological symptoms have returned to baseline levels), no evidence of new or enlarging brain metastases, and has not had CNS surgery or radiotherapy within 4 weeks prior to the first dose, has not undergone stereotactic radiosurgery within 2 weeks, and has discontinued or stabilized steroid dosing within 2 weeks.
•Comorbidities of the following symptoms or conditions prior to the first dose that remain poorly controlled with optimal therapy:
•active uncontrolled systemic bacterial, viral, or fungal infections; pleural, abdominal, or pericardial effusions that are poorly controlled with interventions (e.g., drainage) (poorly controlled is defined as growth that is significant and symptomatic within 2 weeks of fluid collection and requires re-puncturing or other interventions); poorly controlled diabetes mellitus \[fasting blood glucose ≥ 10 mmol/L and/or glycated hemoglobin (HbA1c) ≥ 8%\]; uncontrolled symptomatic hyperthyroidism or hypothyroidism as assessed by the investigators; uncontrolled electrolyte disorders (e.g., hyper/hypocalcemia, hyper/hypomagnesemia, hyper/hypokalemia) as assessed by the investigators; clinically significant severe gastrointestinal disorders as assessed by the investigators, including active ulcerative colitis Crohn's disease, peptic ulcers, or previous surgical procedures that may have significantly interfered with the absorption of the drug.
•Presence of serious cardiovascular disease/abnormalities as indicated by any of the following:
•a QTcF \> 470 msec (females) or \> 450 msec (males) using the Fridericia formula for heart rate correction at screening, (If drug-induced prolongation of the QTcF is suspected, it is assessed by the investigators to be safe and manageable and may be corrected with medication and then enrolled.); left ventricular ejection fraction (LVEF) \< 45%; myocardial infarction or unstable angina pectoris or clinically significant uncontrolled arrhythmia within 6 months prior to the first dose of the drug, including bradyarrhythmias (e.g., type II second or third-degree heart block) that may result in prolongation of the QTcF; classified as class III or IV according to New York Heart Association (NYHA) criteria Congestive heart failure; poorly controlled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg), history of unstable hypertension, or history of poor compliance with antihypertensive therapy.
•Presence of active viral infection or history of:
•Hepatitis B (Hepatitis B surface antigen \[HBsAg\] positive with HBV DNA test \> 2 x 10\^3 IU/mL, eligible for enrollment if re-tested to less than 2 x 10\^3 IU/mL with regular antiviral therapy); positive test for Human Immunodeficiency Virus (HIV) at screening or a known history of other immune deficient disorders; a history of prior organ transplantation, hematopoietic stem cell or bone marrow transplantation therapy.

Arms & Interventions

SY-5007

SY-5007 will be given orally 160 mg twice daily in 28-day cycle continuously until disease progression, death, unacceptable toxicity, or withdraw consent in this study.

Intervention: SY-5007

Outcomes

Primary Outcomes

Assessment of ORR by independent review committee (IRC).

Time Frame: Tumor scans performed at baseline then every 8 weeks up to 1 year, then every 12 weeks thereafter; up to 3 years.

Defined as the number (%) of patients with measurable disease with response of complete response (CR) or partial response (PR) assessed by IRC according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcomes

ORR as assessed by investigators.(Up to 3 years.)
DCR as assessed by investigators and IRC.(Up to 3 years.)
Overall survival (OS).(Up to 3 years.)
PFS as assessed by investigators and IRC.(Up to 3 years.)
Time to response (TTR) as assessed by investigators and IRC.(Up to 3 years.)
DoR as assessed by investigators and IRC.(Up to 3 years.)
Incidence of adverse events (AEs) and serious adverse events (SAEs).(From the screening period to 28 days after treatment completion, up to a maximum of approximately 3 years.)