Immunochemotherapy or Chemotherapy in ALK-rearranged 5'-ALK NSCLC (CLASSIC5)

Chemotherapy Plus Immune Checkpoint Inhibitor With or Without Bevacizumab After Disease Progression With First-line Alectinib of Advanced ALK-rearranged Non-small Cell Lung Cancer With 5'-ALK

This study aimed to investigate the combination of chemotherapy and immunotherapy for patients with metastatic ALK fusion-positive non-small cell lung cancer (NSCLC) who had failed from first line Alectinib. Additionally, available biological samples such as blood and tumor tissues were collected to explore potential biomarkers, including but not limited to RNA-seq, whole-exome sequencing (WES), whole-genome sequencing (WGS), immunohistochemistry, and multiplex immunofluorescence.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab; Drug: Chemotherapy alone or Chemotherapy with or without Bevacizumab

Detailed Description

1. The investigators collected data from patients with metastatic ALK fusion-positive non-small cell lung cancer (NSCLC) who received first-line Alectinib treatment between April 2017 and July 2021. Our analysis aimed to assess their clinical outcomes and explore the impact of 5' ALK on the treatment response to Alectinib.
2. For patients who experienced disease progression after August 2021, they were treated with a combination of chemotherapy and PD-1 monoclonal antibodies with/without Bevacizumab or chemotherapy alone with/without Bevacizumab was observed and recorded data on progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS) for these patients.
3. The investigators collected pre-treatment biological samples for biomarker analysis, including FFPE samples for whole-genome sequencing (WGS), whole-exome sequencing (WES), RNA-seq, and multiplex fluorescence analysis. FFPE samples were also collected for PD-L1 testing. Additionally, pre-treatment blood samples were collected for cytokine analysis, as well as tumor mutational burden (TMB) and T-cell receptor (TCR) testing. The investigators aimed to evaluate the differences in these results between 3' ALK and 5' ALK.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

ALK rearranged Advanced Non-squamous Non-small Cell Lung Cancer Confirmed by NGS

Description

Inclusion Criteria:

1. ≥18，Advanced Non-small Cell Lung Cancer Confirmed by Histopathology
2. ALK -arreaged confirmed by NGS;
3. Received first line treatment Alectinib;
4. Progressed from first-line alectinib;
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.
10. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.

Exclusion Criteria:

1. Patient who do not have the samples for NGS to confirmed ALK status.

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.
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. 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.
9. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
10. Live vaccine was given 2 weeks before the first medication.
11. Women who are breastfeeding or pregnant.
12. Hypersensitivity to the test drug and the ingredients.
13. 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Chemotherapy plus immune checkpoint inhibitors with or without Bevacizumab.; Patients who progressed from first line Alectinib will be treated with chemotherapy plus immune checkpoint inhibitors with or without Bevacizumab following the patients' preferences.	Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab; Immune Checkpoint Inhibitors, for pembrolizumab, 200mg ivgtt once,every 21 days; for Atezolizumab, 1200mg vgtt once,every 21 days.; Other Names: Bevacizumab
Experimental: Arm B: Chemotherapy with or without Bevacizumab.; Patients who progressed from first line Alectinib will be treated with chemotherapy with or without Bevacizumab following the patients' preferences.	Drug: Chemotherapy alone or Chemotherapy with or without Bevacizumab; Bevacizumab, 15mg/kg，every 21 day; Other Names: Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression free survival time	From first dose until 28 days after the last dose, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival time	Time from first subject dose to study completion, or up to 48 months

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): April 14, 2017
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: July 31, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Non-small Cell Lung Cancer; Alectinib; ALK Rearranged
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Immune Checkpoint Inhibitors
• Other Study ID Numbers: ALICE (EC11-527)

Drug and device information, study documents

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