Non-small Cell Lung CancerPhase 2CLASSIC5NCT04997382
Chemotherapy Combined with ICIs in First-line Alectinib Failed Patients with ALK-rearranged NSCLC
A Phase 2 study testing Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab and Chemotherapy alone or Chemotherapy with or without Bevacizumab in people with Non-small Cell Lung Cancer, run by Hunan Province Tumor Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab and Chemotherapy alone or Chemotherapy with or without Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteChina
- Study dates
- 17 Aug 2021to 31 Jan 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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;
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Chemotherapy Combined with Immune Checkpoint Inhibitors in Patients with ALK-rearranged Non-small Cell Lung Cancer (NSCLC) Who Have Progressed After First-line Alectinib: a Proof-of-concept, Phase 2 Trial
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.
Read the detailed description
- 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.
- 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.
- 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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab, Chemotherapy alone or Chemotherapy with or without Bevacizumab
- Keywords
- Non-small Cell Lung Cancer, Alectinib, ALK Rearranged
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without BevacizumabDrug
Also called Bevacizumab
Immune Checkpoint Inhibitors, for pembrolizumab, 200mg ivgtt once,every 21 days; for Atezolizumab, 1200mg vgtt once,every 21 days.
Chemotherapy alone or Chemotherapy with or without BevacizumabDrug
Also called Bevacizumab
Bevacizumab, 15mg/kg，every 21 day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab; Drug: Chemotherapy alone or Chemotherapy with or without Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Progression free survival time
Measured: From first dose until 28 days after the last dose, up to 24 months
Secondary outcomes (2)
OS
Overall survival time
Measured: Time from first subject dose to study completion, or up to 48 months
ORR
Objective Response Rate
Measured: From first dose until 28 days after the last dose, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start17 Aug 2021
- Primary completion31 Jan 2024
- Study completion31 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hunan Province Tumor Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongchang Zhang, Hunan Province Tumor Hospital
- Investigators
- Yongchang Zhang, MD, Principal investigator, Hunan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04997382
- Sponsor's protocol ID
- ALICE
- Acronym
- CLASSIC5
- Status last verified
- May 2024
- First submitted
- 31 Jul 2021
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemotherapy Combined with Immune Checkpoint Inhibitors in Patients with ALK-rearranged Non-small Cell Lung Cancer (NSCLC) Who Have Progressed After First-line Alectinib: a Proof-of-concept, Phase 2 Trial
- ClinicalTrials.gov ID
- NCT04997382
- Acronym / sponsor ID
- CLASSIC5 / ALICE
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Non-small Cell Lung Cancer, Alectinib, ALK Rearranged
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Hunan Province Tumor HospitalUniversity, hospital or other
- Study start
- 17 Aug 2021 (actual)
- Primary completion
- 31 Jan 2024 (actual)
- Study completion
- 31 Jan 2024 (actual)
- First posted
- 9 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Part A: Patients with 3'ALK retained 5'ALK. | Experimental | Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab, Drug: Chemotherapy alone or Chemotherapy with or without BevacizumabPatients 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. |
| Part B: Patients with 3'ALK. | Experimental | Drug: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab, Drug: Chemotherapy alone or Chemotherapy with or without BevacizumabPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥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;
Key exclusion criteria (15 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without BevacizumabAlso: BevacizumabImmune Checkpoint Inhibitors, for pembrolizumab, 200mg ivgtt once,every 21 days; for Atezolizumab, 1200mg vgtt once,every 21 days. | Drug | Part A: Patients with 3'ALK retained 5'ALK., Part B: Patients with 3'ALK. |
| Chemotherapy alone or Chemotherapy with or without BevacizumabAlso: BevacizumabBevacizumab, 15mg/kg，every 21 day | Drug | Part A: Patients with 3'ALK retained 5'ALK., Part B: Patients with 3'ALK. |
Primary outcome
PFS
Time frame: From first dose until 28 days after the last dose, up to 24 months
Progression free survival time
2 secondary outcomes
OS
Time frame: Time from first subject dose to study completion, or up to 48 months
ORR
Time frame: From first dose until 28 days after the last dose, up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yongchang Zhang, MD principal investigator
Hunan Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab and Chemotherapy alone or Chemotherapy with or without Bevacizumab in people with Non-small Cell Lung Cancer, run by Hunan Province Tumor Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: From first dose until 28 days after the last dose, up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.