A Phase II, Open-Label, Single-Arm, Multicenter Study of Efficacy and Safety of SY-3505 in Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer Who Have Progressed On or Are Intolerant to Second-Generation ALK TKI

Shouyao Holdings (Beijing) Co. LTD1 site in 1 country153 target enrollmentJune 30, 2023

ConditionsNon-small-cell Lung Carcinoma

InterventionsSY-3505

DrugsSY-3505

Overview

Phase: Phase 2
Intervention: SY-3505
Conditions: Non-small-cell Lung Carcinoma
Sponsor: Shouyao Holdings (Beijing) Co. LTD
Enrollment: 153
Locations: 1
Primary Endpoint: Objective Response Rate (ORR) assessed by the 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 an open-label, single-arm, multicenter, phase II study to evaluate the efficacy and safety of SY-3505 capsule in patients with locally advanced or metastatic NSCLC who have progressed on or are intolerant to second-generation ALK tyrosine kinase inhibitor (TKI).

Detailed Description

SY-3505 is a potent, brain-penetrant, third-generation ALK tyrosine kinase inhibitor (TKI) with preclinical activity against both wild-type and most known resistance mutations of ALK occurring in first-generation and second-generation ALK TKI-resistant patients. In this phase 2 study, patients with locally advanced or metastatic NSCLC who have progressed on or are intolerant to second-generation ALK TKI will be treated with SY-3505 capsules at 600 mg once daily (QD) orally until disease progression, refusal or unacceptable toxicity. Cycles of treatment are every 21 days with continuous dosing of SY-3505. During the study, patients will be followed-up for safety and efficacy evaluation at study protocol defined time points.

Registry

clinicaltrials.gov

Start Date

June 30, 2023

End Date

June 10, 2025

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

•Patients must meet all of the following criteria to be eligible to participate in this study:
•Age ≥ 18 years at the time of signing the informed consent form (ICF).
•Histologically or cytologically confirmed locally advanced (tumor lesion could not be radically cued by surgery or radiation as asessed by the investigators) or metastatic NSCLC.
•Prior treated with at least one second-generation ALK TKI (including unmarketed investigational drugs) and imaging evidence of disease progression (PD) or intolerance to prior treatment toxicity.
•Agree to provide fresh tumor tissue samples to test positive for ALK fusion (ALK-positive) by the central laboratory:
•If the patient is indeed unable to provide fresh tumor tissue samples (e.g., repuncture has been assessed by the investigator as having a higher clinical risk) and cannot provide archived tissue samples within 2 years prior to initial administration, but can provide ALK-positive testing reports within 2 years prior to the first administration (detection methods include FISH, RT-PCR, IHC \[Ventana method\] or NGS, etc.), inclusion or not of the patient will be discussed and decided by the investigator and the sponsor;
•If the patient is indeed unable to provide either fresh tumor tissue samples (e.g., repuncture has been assessed by the investigator as having a higher clinical risk) or ALK-positive testing reports within 2 years prior to the first administration, but can provide archived tissue samples within 2 years prior to the first administration and confirmed as ALK-positive by the central laboratory, inclusion or not of the patient will be discussed and decided by the investigator and the sponsor.
•Must have at least one extracranial target lesion that meets the RECIST 1.1 criteria; For a lesion that has previously received radiotherapy, it can be assessed as a target lesion only when it shows definite progression after radiotherapy.
•Eastern Cooperative Oncology Group (ECOG) performance status 0-
•Estimated Life expectancy ≥ 3 months.

Exclusion Criteria

•Patients who meet any of the following criteria are not eligible to participate in this study:
•Patients with known driver alterations other than ALK, such as EGFR, MET, RET, ROS1, NTRK, etc. (If ALK co-mutation exists, the patient can discuss with the investigator for enrollment);
•Previous treated with any third-generation ALK TKI (including marketed drugs such as loratinib, and unmarketed investigational drugs);
•History of allergy to any component or excipient of SY-3505 capsules;
•With other primary malignancies, except those that have been cured and have not recurred within 2 years prior to screening, and those that have been cured of basal or squamous cell carcinoma of the skin, carcinoma in situ of cervix, or carcinoma in situ of breast;
•The presence of symptomatic primary CNS tumors, symptomatic CNS metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Except: Patient had stable CNS disease (no evidence of progression identified by imaging for at least 4 weeks prior to initial administration, and all neurological symptoms had recovered to baseline), no evidence of new or progressive brain metastases, no CNS surgery or radiotherapy within 4 weeks prior to initial administration, and no stereotactic radiosurgery (SRS) within 2 weeks prior to initial administration. Steroid administration was stopped or the dose stabilized within 2 weeks prior to initial administration. (This exception does not include cancerous meningitis, which should be excluded regardless of clinically stable conditions).
•The following symptoms or diseases occurred prior to initial administration and remain poorly controlled after optimal treatment:
•Systemic bacterial, viral or fungal infection with uncontrolled activity;
•Poorly controlled (poorly control refers to the effusion increases significantly within 2 weeks after extraction, with obvious symptoms, requiring further puncture or other intervention) pleural effusion, abdominal effusion or pericardial effusion after intervention (such as drainage) ;
•Poorly controlled diabetes (fasting blood glucose ≥11.1 mmol/L and/or HbA1c ≥ 8%);

Arms & Interventions

SY-3505-Phase II

SY-3505 single agent, 600 mg oral capsules, QD, continuously

Intervention: SY-3505

Outcomes

Primary Outcomes

Objective Response Rate (ORR) assessed by the independent review committee (IRC)

Time Frame: Up to 2 years

ORR is defined as the proportion of patients achieving an objective response (complete response \[CR\] or partial response \[PR\]) according to Response Evaluation Criteria in Solid Tumors (RECIST), v.1.1 (RECIST 1.1).

Secondary Outcomes

Intracranial Objective Response Rate (IC-ORR) assessed by the investigator and IRC(Up to 2 years)
Intracranial Disease Control Rate (IC-DCR) assessed by the investigator and IRC(Up to 2 years)
Intracranial Duration of Response (IC-DoR) assessed by the investigator and IRC(Up to 2 years)
Overall Survival(Up to 2 years)
Incidence of Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5(Up to 2 years)
Disease Control Rate (DCR) assessed by the investigator and IRC(Up to 2 years)
ORR assessed by the investigator(Up to 2 years)
Progression-Free Survival (PFS) assessed by the investigator and IRC(Up to 2 years)
Time to Tumor Response (TTR) assessed by the investigator and IRC(Up to 2 years)
Duration of Response (DoR) assessed by the investigator and IRC(Up to 2 years)