Chemotherapy Combined with ICIs in First-line Alectinib Failed Patients with ALK-rearranged NSCLC

NCT04997382 | Completed Phase 2

• 1 other identifier: ALICE
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small Cell Lung Cancer; Alectinib; ALK Rearranged

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression free survival time

  From first dose until 28 days after the last dose, up to 24 months

Secondary Outcomes (2)

• OS

  Time from first subject dose to study completion, or up to 48 months

• ORR

  From first dose until 28 days after the last dose, up to 24 months

Study Arms (2)

Part A: Patients with 3'ALK retained 5'ALK.

EXPERIMENTAL

Patients with 3'ALK retained 5'ALK who progressed from first line Alectinib were randomized to Arm A: Chemo+ICIs/Chemo+ICIs+BEV and Arm B: Chemo/Chemo+BEV.

Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab; Drug: Chemotherapy alone or Chemotherapy with or without Bevacizumab

Part B: Patients with 3'ALK.

EXPERIMENTAL

Patients with 3'ALK who progressed from first line Alectinib were randomized to Arm C: Chemo+ICIs/Chemo+ICIs+BEV and Arm D: Chemo/Chemo+BEV.

Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab; Drug: Chemotherapy alone or Chemotherapy with or without Bevacizumab

Interventions

Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab DRUG

Immune Checkpoint Inhibitors, for pembrolizumab, 200mg ivgtt once,every 21 days; for Atezolizumab, 1200mg vgtt once,every 21 days.

Also known as: Bevacizumab

Part A: Patients with 3'ALK retained 5'ALK.; Part B: Patients with 3'ALK.

Chemotherapy alone or Chemotherapy with or without Bevacizumab DRUG

Bevacizumab, 15mg/kg，every 21 day

Also known as: Bevacizumab

Part A: Patients with 3'ALK retained 5'ALK.; Part B: Patients with 3'ALK.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18，Advanced Non-small Cell Lung Cancer Confirmed by Histopathology
• ALK -arreaged confirmed by NGS;
• Received first line treatment Alectinib;
• Progressed from first-line alectinib;
• ECOG 0-1;
• Predicted survival ≥ 12 weeks;
• Adequate bone marrow hematopoiesis and organ function;
• Presence of measurable lesions according to RECIST 1.1;
• Subjects with stable brain metastases may be included in the study.
• Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.

You may not qualify if:

• Patient who do not have the samples for NGS to confirmed ALK status.
• 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.
• Presence of spinal cord compression or meningeal metastasis.
• History of other malignant tumors within 2 years.
• 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.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• 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.
• Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
• Live vaccine was given 2 weeks before the first medication.
• Women who are breastfeeding or pregnant.
• Hypersensitivity to the test drug and the ingredients.
• Other conditions assessed by the investigator to be unsuitable for participation in the study.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immune Checkpoint Inhibitors; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Yongchang Zhang, MD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Based on the treatment preferences of each patient, they received either chemotherapy alone or in combination with immune checkpoint inhibitors, as well as chemotherapy in combination with immune checkpoint inhibitors (ICI), either with or without bevacizumab.

Study Record Dates

• First Submitted: July 31, 2021
• First Posted: August 9, 2021
• Study Start: August 17, 2021
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: February 25, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)