An Open-label, Fixed-sequence Phase I Clinical Trial to Evaluate the Effect of HS-10504 on the Pharmacokinetics of Midazolam in Patients With Non-small Cell Lung Cancer

NCT07685041 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: HS-10504-113
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, fixed-sequence Phase I clinical trial to evaluate the effect of HS-10504 on the pharmacokinetics of midazolam (CYP3A4 substrate) in patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have experienced disease progression during or after treatment with EGFR-TKIs.

Conditions

NSCLC

Keywords

Phase I; Drug interaction; HS-10504; NSCLC

Outcome Measures

Primary Outcomes (3)

• Evaluation of PK parameters of Midazolam: Cmax

  To evaluate the Cmax of Midazolam administered alone and in combination with HS-10504

  24 hours after administration of Midazolam

• Evaluation of PK parameters of Midazolam: AUC0-t

  To evaluate the AUC0-t of Midazolam administered alone and in combination with HS-10504

  24 hours after administration of Midazolam

• Evaluation of PK parameters of Midazolam: AUC0-∞

  To evaluate the AUC0-∞ of Midazolam administered alone and in combination with HS-10504

  24 hours after administration of Midazolam

Secondary Outcomes (29)

• Evaluation of PK parameters of Midazolam: Tmax

  24 hours after administration of Midazolam

• Evaluation of PK parameters of Midazolam: t1/2z

  24 hours after administration of Midazolam

• Evaluation of PK parameters of Midazolam: λz

  24 hours after administration of Midazolam

• Evaluation of PK parameters of Midazolam: CLz/F

  24 hours after administration of Midazolam

• Evaluation of PK parameters of Midazolam: Vz/F.

  24 hours after administration of Midazolam

Study Arms (1)

Experimental group

EXPERIMENTAL

Drug-drug interaction Arm

Drug: HS-10504； midazolam

Interventions

HS-10504； midazolam DRUG

HS-10504：Participants receive HS-10504 tablets 400 mg (100 mg/tablet, 4 tablets) once daily Midazolam：Participants receive a single oral dose of midazolam oral solution 1 mg (2 mg/mL, 0.5 mL) on C0D1 and C2D20, respectively。

Experimental group

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed locally advanced or metastatic NSCLC
• Disease progression or intolerance to prior third-generation EGFR TKI therapy in patients with mNSCLC
• Confirmed EGFR mutation positivity in participants before enrollment.
• At least one target lesion according to RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 with no deterioration in the 2 weeks prior to the first dose
• Minimum life expectancy greater than 12 weeks
• Female participants of childbearing potential must agree to use appropriate contraception (refer to section 12.5) from the time of signing informed consent until 6 months after the last dose, and should not breastfeed; male participants must agree to use barrier contraception (i.e., condoms) from the time of signing informed consent until 6 months after the last dose
• Willing to participate in this clinical trial, understand the study procedures, and be able to provide written informed consent.

You may not qualify if:

• Has received or is currently receiving the following treatments:
• Prior or current treatment with a fourth-generation EGFR tyrosine kinase inhibitor.
• Use of strong/moderate inhibitors or strong/moderate inducers of CYP3A4, CYP3A5, CYP2C8, and/or CYP2D6, or narrow therapeutic index drugs that are sensitive substrates of CYP3A4, CYP3A5, P-gp, and BCRP within 14 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product; or need to continue these medications during the study period.
• Use of drugs that affect gastric acid secretion or intragastric pH within 7 days prior to the first dose of investigational product.
• Currently receiving treatment with drugs known to prolong the QT interval or that may cause torsade de pointes; or need to continue these medications during the study period
• Presence of toxicities from prior anti-tumor therapy that have not resolved to \< Grade 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• History of other primary malignancies.
• Inadequate bone marrow reserve or hepatic/renal organ function.
• Meets any of the following cardiac criteria:
• Mean Fridericia-corrected QT interval (QTcF) \> 470 msec on resting electrocardiogram (ECG);
• Resting ECG shows any clinically significant rhythm, conduction, or ECG morphological abnormality deemed important by the investigator (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, and PR interval \> 250 msec, etc.);
• Presence of any factors that increase the risk of QT prolongation or arrhythmic events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication that prolongs the QT interval;
• Left ventricular ejection fraction (LVEF) \< 50%.
• Severe, uncontrolled, or active cardiovascular disease.
• Severe or poorly controlled diabetes mellitus.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: July 6, 2026
• Study Start: June 27, 2026
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): July 20, 2027
• Last Updated: July 6, 2026

Record last verified: 2026-06