ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma (ATPase)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Crizotinib

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongchang Zhang, MD; Phone Number: 7+861383123436 +8613873123436; Email: zhangyongchang@csu.edu.cn
• Study Contact Backup: Name: Nong Yang, MD; Phone Number: +8613873123436 +8613873123436; Email: yangnong0217@163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Yongchang Zhang, MD; Phone Number: +86 731 89762323; Email: zhangyongchang@csu.edu.cn
      • Contact: Nong Yang, MD; Phone Number: +86 731 89762321; Email: yangnong0217@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Study Population

ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A, first line ALK-TKIs; All the patients were treated with first line ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.	Drug: Crizotinib; Crizotinib 250mg po bid Aectinib 600mg po bid Lorlatinib 100mg po qd Brigatinib, 90mg po qd for one week and than 180mg po qd forever Pemetrexed 500mg/m2; Other Names: Carboplatin; Paclitaxel; Pemetrexed; Lorlatinib; Alectinib; Brigatinib; immune checkpoint inhibitors
Experimental: Cohort B, second line ALK-TKIs; All the patients were treated with second line ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.	Drug: Crizotinib; Crizotinib 250mg po bid Aectinib 600mg po bid Lorlatinib 100mg po qd Brigatinib, 90mg po qd for one week and than 180mg po qd forever Pemetrexed 500mg/m2; Other Names: Carboplatin; Paclitaxel; Pemetrexed; Lorlatinib; Alectinib; Brigatinib; immune checkpoint inhibitors
Experimental: Cohort C, post second line ALK-TKIs; All the patients were treated with post second ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.	Drug: Crizotinib; Crizotinib 250mg po bid Aectinib 600mg po bid Lorlatinib 100mg po qd Brigatinib, 90mg po qd for one week and than 180mg po qd forever Pemetrexed 500mg/m2; Other Names: Carboplatin; Paclitaxel; Pemetrexed; Lorlatinib; Alectinib; Brigatinib; immune checkpoint inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	To assess progression-free survival of patients treated by different treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as first dose to first documented disease progression assessed by investigator or death due to any cause	Time from first subject dose to study completion, or up to 36 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To assess overall survival, define as first dose to the death of the subject due to any cause	Time from first subject dose to study completion, or up to 36 month.
Objective Response Rate (ORR)	To assess ICI and TKIs overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as the proportion of subjects who have a complete response (CR) or a partial response (PR)	Time from first dose to last dose, or up to 24 month.

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Investigators: Principal Investigator: Yongchang Zhang, MD, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 8, 2027

Study Registration Dates

• First Submitted: August 14, 2021
• First Submitted That Met QC Criteria: August 14, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Squamous cell lung cancer; ALK rearrangement; ALK-TKI
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Carboplatin; Paclitaxel; Pemetrexed; Immune Checkpoint Inhibitors; Crizotinib; Alectinib
• Other Study ID Numbers: 20210119

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No