Clinical trial NCT05014464: ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma
Official title: Molecular Characterization and Clinical Outcomes of ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: ALK rearrangement
Squamous cell lung cancer
ALK-TKI
Lead sponsor: Hunan Province Tumor Hospital
Sponsor class: OTHER
First posted: 2021-08-20
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was to explore the efficacy of ALK-TKI in lung squamous cell carcinoma. Approximately 5% of lung adenocarcinomas have oncogenic fusions of EML-4 and ALK a mutation associated with tumorigenesis and migration.

Detailed description: This research focuses on exploring epidemiology, distributions and the efficacy and prognosis of ALK-TKI in lung squamous cell carcinoma.Approximately 5% of lung adenocarcinomas have oncogenic fusions of EML-4 and ALK a mutation associated with tumorigenesis and migration. Several studies have shown that in patients with ALK-rearranged non-small cells, the use of ALK inhibitors can achieve better efficacy and significantly prolong overall survival. However few of them performed Fish or NGS tests. Our data demonstrates that lung squamous cell carcinoma with ALK rearrangement responds well to ALK-TKI, and correspondingly has a significant improvement in survival time and prognosis, providing a basis for the treatment of ALK-positive patients with lung squamous cell carcinoma. At the same time, we believe that genetic testing is also required for lung squamous cell carcinoma to achieve more accurate medication.

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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Time from first subject dose to study completion, or up to 36 month
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Time from first subject dose to study completion, or up to 36 month.
measure: Objective Response Rate (ORR)
timeFrame: Time from first dose to last dose, or up to 24 month.
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Hunan Cancer Hospital
name: Yongchang Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: