Testing HSK40118 in patients with advanced lung cancer and EGFR mutations

A Phase I, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of HSK40118 in Patients With EGFR Mutation Locally Advanced or Metastatic NSCLC

This study is testing a new oral medication called HSK40118 to see if it is safe and effective for people with advanced lung cancer that has a specific genetic mutation.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Haisco Pharmaceutical Group Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 12 sites (Beijing, Beijing Municipality and 11 other locations)
• Trial ID: NCT06050980 on ClinicalTrials.gov

What this trial studies

This phase I study evaluates the safety and tolerability of HSK40118, an oral medication, in patients with advanced non-small cell lung cancer (NSCLC) who have an active EGFR mutation. The study consists of two phases: a dose escalation phase to determine the optimal dosage and a dose expansion phase to further assess the drug's effects. Patients will be monitored for pharmacokinetics (PK) and pharmacodynamics (PD) to understand how the drug behaves in the body and its potential therapeutic effects.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable locally advanced or metastatic NSCLC and a history of treatment with EGFR-TKIs.

Not a fit: Patients with early-stage NSCLC or those who have not previously been treated with EGFR-TKIs may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced NSCLC who have specific genetic mutations.

How similar studies have performed: Other studies have shown promise with similar EGFR-targeted therapies, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years, Male and female patients, at time of signing informed consent form (ICF).
2. ECOG=0-1, with no deterioration in 2 weeks before first dose of HSK40118.
3. Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.
4. Patients will provide blood or tumor sample according to their own willingness.
5. Patients in Phase Ia and Ib will fulfill the different criteria of the following:

   Phase Ia(Part A): Previous treatment with at least one EGFR-TKI, including 1st, 2nd and 3rd-generation EGFR-TKI; Phase Ia(Part B)/Phase Ib: Previous treatment with 3rd-generation EGFR-TKI.
6. tumour lesions/lymph nodes: Phase Ia(Part A): Patients should have at least one assessable tumour lesions/malignant lymph nodes; Phase Ia(Part B) /Phase Ib: Patients should have at least one measurable tumour lesions/malignant lymph nodes.
7. Life expectancy ≥ 3 months.
8. Adequate hematologic and organ function per protocol.
9. Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must use highly effective contraception per protocol throughout and after 90 days of the last dose of the study.

Exclusion Criteria:

1. malignant tumor within 5 years, with the exception of cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, or other tumors with low malignancy.
2. Unstable spinal cord compression or brain metastases per protocol.
3. Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
4. Prior treatment with 4th-generation EGFR-TKIs(TKI for 3th-generation resistance).
5. Treatment with any of the following:

   Prior treatment with an EGFR-TKI or other small-molecule anti-tumor drug within 7 days or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter; Prior treatment with chemotherapy, palliative radiotherapy, or Herbal therapy within 2 weeks or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter; Prior treatment with radiotherapy, immunotherapy/biotherapy therapy, or other pharmaceutical clinical trial within 4 weeks or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter.
6. Treatment with inhibitors for P-glycoprotein (P-gp) within 7 days prior to the first dose of HSK40118.
7. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia, dermal toxicity, and other toxicity considering no safety risks by investigator.
8. Any disease which would cause chronic diarrhea, eg. Crohn's disease, or irritable bowel syndrome.
9. Any disease which would preclude drug absorption, metabolism or pharmacokinetics, eg. active peptic ulcer or chronic gastroesophageal reflux disease.
10. Any severe disease of respiratory system, eg. interstitial lung disease, radiation pneumonitis, drug-induced pneumonitis, or uncontrolled asthma.
11. Patient who have clinically significant or uncontrolled cardiac disease, include: QTc interval ≥ 450(male)/470(female) msec; any clinically significant arrhythmia; left ventricular ejection fraction \< 50%; myocardial infarction, unstable angina, or class III/IV cardiac failure by the NYHA that occurred within 6 months prior to the first dose of HSK40118.
12. Any thromboembolic events within 6 months prior to the first dose of HSK40118; any familial or aquired thrombophilia.
13. Active bleeding at screening, history of visceral hemorrhage within 3 months prior to the first dose of HSK40118, or visceral bleeding tendency within 6 months prior to the first dose of HSK40118.
14. Patient who is undergoing, or receiving long-term(\> 6 months) anticoagulant/antiplatelet therapy; receiving drugs affecting coagulation function 1 week prior to the first dose of HSK40118.
15. INR, APTT \> 1.5xULN, or any bleeding tendency or coagulopathy at screening.
16. Uncontroled hypertension(systolic pressure ≥160mmHg, or diastolic pressure ≥100mmHg).
17. Any unstable systemic disease, eg. severe metabolic disease: liver cirrhosis, renal failure, or uremia.
18. Any disease of the eyes \> CTCAE v5.0 Grade 1.
19. Autologous transplantation surgery within 3 months prior to the first dose of HSK40118; Allogeneic transplantation, or stem-cell Transplant surgery within 6 months prior to the first dose of HSK40118; Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of HSK40118.
20. Patients with HIV, HBV or HCV infection.
21. Patients with active syphilis infection.
22. Patients who have an uncontroled systematic infection, eg. fungal, bacterial, or virus infection.
23. Patients who would interfere with cooperation or outcome-assessment of the trial.
24. Allergic to any HSK40118 active constituent or ingredients.
25. (Child-bearing period women only)Patients testing positive for pregnancy, or during lactation.
26. Any other circumstances that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Where this trial is running

Beijing, Beijing Municipality and 11 other locations

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)
• Chongqing Cancer Hospital — Chongqing, Chongqing Municipality, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Recruiting)
• First Affiliated Hospital of Henan University of Science and Technology — Luoyang, Henan, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Shandong Cancer Hospital — Jinan, Shandong, China (Recruiting)
• Shanghai Pulmonary Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Taizhou hospital of Zhejiang Province — Taizhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Fangqiong Li

Conditions NSCLC