Using ALK inhibitors for advanced squamous cell lung cancer

Molecular Characterization and Clinical Outcomes of ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma

This study is testing if a medication called Crizotinib can help people with advanced squamous cell lung cancer that has a specific genetic change to live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (Academic / other)
• Drugs / interventions: sunvozertinib, anlotinib, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT05014464 on ClinicalTrials.gov

What this trial studies

This research investigates the effectiveness of ALK tyrosine kinase inhibitors (ALK-TKIs) in treating advanced squamous cell carcinoma of the lung that is positive for ALK rearrangement. The study aims to evaluate the epidemiology, distribution, and prognosis of patients with this specific mutation, as well as the impact of genetic testing on treatment accuracy. By focusing on patients with confirmed ALK fusions, the study seeks to demonstrate improved survival rates and overall efficacy of ALK-TKIs compared to traditional treatments. The intervention involves administering Crizotinib to eligible participants who meet specific criteria.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed ALK fusion positive advanced squamous cell carcinoma who have not received prior systemic treatment.

Not a fit: Patients with prior systemic therapy for locally advanced or metastatic disease or those who have received certain treatments within specified timeframes may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with ALK-rearranged advanced squamous cell lung cancer.

How similar studies have performed: Previous studies have shown promising results with ALK inhibitors in similar patient populations, indicating a potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
2. Age ≥ 18 years.
3. Histopathology or cytology confirmed and recorded local progression or metastatic Advanced Squamous Cell Carcinoma without systemic treatment.
4. ALK fusion positive evaluated by IHC (ventana), NGS or FISH.
5. ECOG 0 - 1.
6. Predicted survival ≥ 12 weeks.
7. Adequate bone marrow hematopoiesis and organ function
8. Presence of measurable lesions according to RECIST 1.1.
9. Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

1. Prior systemic therapy for locally advanced or metastatic disease.
2. Subjects who have received any of the following treatments must be excluded:

   * Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
   * Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
   * Ongoing (or inability to discontinue) possibly potent CYP1A2, CYP3A inhibitor (1 week), or inducer (2 weeks) drug therapy or herbal supplements within 1-2 weeks prior to the first dose.
3. Presence of spinal cord compression or meningeal metastasis.
4. History of other malignant tumors within 2 years.
5. Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
8. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
9. Heart-related diseases or abnormalities
10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
12. Live vaccine was given 2 weeks before the first medication.
13. Women who are breastfeeding or pregnant.
14. Hypersensitivity to the test drug and the ingredients.
15. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Where this trial is running

Changsha, Hunan

• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)

Study contacts

• Principal investigator: Yongchang Zhang, MD — Hunan Cancer Hospital
• Study coordinator: Yongchang Zhang, MD

Conditions Non-small Cell Lung Cancer; ALK rearrangement; Squamous cell lung cancer; ALK-TKI