Non-Small Cell Lung CancerPhase 3UPLIFTNCT06955325
Umbrella Trial of Adjuvant Therapy in Completely Resected High-risk Stage IA-IB NSCLC: Focus on Driver Mutations
A Phase 3 study testing Icotinib, Rezivertinib and Ensartinib in people with Non-Small Cell Lung Cancer, run by The First Affiliated Hospital of Guangzhou Medical University.
Trial summary
This study explores how adjuvant therapy affects survival in completely resected high-risk stage IA-IB NSCLC patients with different driver gene mutations. 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?
- Icotinib, Rezivertinib and Ensartinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- No sites listed yet
- Study dates
- May 2025to Dec 2035
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Age 18-75 years and able to provide written informed consent.
- Primary non-squamous NSCLC confirmed by pathology, with no brain metastases.
- Complete R0 surgical resection (lobectomy, segmentectomy, or pneumonectomy) of stage IA or IB NSCLC (AJCC 8th edition).
- High-risk disease (one or more): low differentiation, solid/micropapillary/complex glandular patterns, vascular invasion, visceral pleural invasion, alveolar space spread, or intermediate/high risk on 14-gene test.
- Documented driver gene status (EGFR mutation, ALK/ROS1 fusion, or wild-type) via postoperative tumor sample.
- ECOG performance status 0 or 1, with stable condition over the last two weeks.
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- Surgery within 4-10 weeks before starting treatment, with full recovery.
- Adequate organ function as per protocol-defined labs.
- Negative pregnancy test (if applicable) and use of effective contraception during and 3 months after treatment.
Who cannot join
- Evidence of unresectable/metastatic NSCLC, incomplete resection (R1/R2), or wedge resection only.
- Prior systemic therapy (e.g., chemotherapy, targeted therapy, immunotherapy) for the current NSCLC.
- Major surgery (excluding lung cancer surgery) within 3 weeks before first study dose.
- Planned concurrent anti-cancer therapy (chemo, radiotherapy, or targeted therapy) during the study.
- Clinically significant cardiac disorders (e.g., poorly controlled hypertension, recent MI or stroke, prolonged QTc).
- History or suspicion of interstitial lung disease requiring treatment.
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- Active or uncontrolled infection (e.g., hepatitis B with detectable HBV DNA, hepatitis C, HIV, active TB).
- Severe GI conditions impairing drug absorption (e.g., Crohn's, ulcerative colitis).
- Use of strong CYP3A inducers/inhibitors within 1 week or ongoing need for warfarin.
- Participation in another interventional trial within 4 weeks or receipt of a live vaccine within 180 days.
- Any condition that may compromise adherence or safety, per investigator judgment.
About this study
Official title: A Randomized, Phase III Umbrella Trial of Adjuvant Therapy Versus Observation in Completely Resected High-Risk Stage IA-IB Non-Small Cell Lung Cancer Based on Oncogenic Driver Mutations
This study explores how adjuvant therapy affects survival in completely resected high-risk stage IA-IB NSCLC patients with different driver gene mutations.
Read the detailed description
This study aims to evaluate whether tailored, targeted therapy or immunotherapy can effectively prevent cancer recurrence in patients with early-stage (stage IA-IB) non-small cell lung cancer (NSCLC) who have undergone complete surgical resection but are at high risk of recurrence. Based on each patient's specific driver gene mutation status (e.g., EGFR or ALK/ROS1) or wild-type status, participants will receive either targeted therapy or immunotherapy compared to routine follow-up (observation). The goal is to see if these approaches can improve disease-free survival and potentially reduce the risk of lung cancer recurrence.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Icotinib, Rezivertinib, Ensartinib, Benmelstobart
- 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.
IcotinibDrug
Oral icotinib tablets (125 mg) administered three times daily (TID) for up to 1 year or until disease recurrence or unacceptable toxicity. Icotinib is an EGFR tyrosine kinase inhibitor targeting EGFR-sensitizing mutations.
RezivertinibDrug
Oral rezivertinib capsules (100 mg) taken once daily (QD) for up to 1 year or until disease recurrence or unacceptable toxicity. Rezivertinib is an EGFR tyrosine kinase inhibitor targeting EGFR-sensitizing mutations.
EnsartinibDrug
Oral ensartinib capsules (225 mg) taken once daily (QD) for up to 1 year or until disease recurrence or unacceptable toxicity. Ensartinib is an ALK/ROS1 tyrosine kinase inhibitor designed to inhibit ALK/ROS1 fusion-driven NSCLC.
BenmelstobartDrug
Intravenous infusion of bemosumab 1200 mg every 3 weeks (Q3W). Treatment continues for up to 4 cycles initially, and may be extended (maintenance) for up to 3 years or until disease recurrence or unacceptable toxicity. Bemosumab is a monoclonal antibody under investigation for immunotherapy in NSCLC.
| Study group | Role | What they receive |
|---|---|---|
| Adjuvant therapy | Experimental | Not described Receives: Drug: Icotinib; Drug: Rezivertinib; Drug: Ensartinib; Drug: Benmelstobart |
| Observation | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Free Survival (DFS)
Disease-free survival (DFS) is defined as the time from randomization to the first documented disease recurrence (local relapse or distant metastasis confirmed by imaging or pathology) or death from any cause, whichever occurs first. Participants without documented recurrence or death at the time of analysis will be censored at their last disease assessment date.
Measured: From randomization until disease recurrence or death (up to approximately 5 years)
Secondary outcomes (3)
Overall Survival (OS)
Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who remain alive or are lost to follow-up at the time of analysis will be censored at the date of last contact.
Measured: From randomization to death or last follow-up (up to approximately 5 years)
Central Nervous System Disease-Free Survival (CNS DFS)
CNS DFS is defined as the time from randomization to the date of first occurrence of central nervous system (CNS) metastases or death from any cause, whichever occurs first, as determined by imaging or clinical assessment. Participants without a CNS event or death at the time of analysis will be censored at their last disease assessment date.
Measured: From randomization until CNS progression or death, whichever occurs first (up to approximately 5 years)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
AEs graded by CTCAE version 5.0
Measured: From date of randomization up to approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2025
- Study startMay 2025 (estimated)
- Primary completionDec 2030 (estimated)
- Study completionDec 2035 (estimated)
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.
- More trials run by The First Affiliated Hospital of Guangzhou Medical UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianxing He, The First Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06955325
- Sponsor's protocol ID
- UPLIFT
- Acronym
- UPLIFT
- Status last verified
- May 2025
- First submitted
- 16 Apr 2025
- Last updated
- 6 May 2025
- Results posted
- 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 6 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Phase III Umbrella Trial of Adjuvant Therapy Versus Observation in Completely Resected High-Risk Stage IA-IB Non-Small Cell Lung Cancer Based on Oncogenic Driver Mutations
- ClinicalTrials.gov ID
- NCT06955325
- Acronym / sponsor ID
- UPLIFT / UPLIFT
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- May 2025 (estimated)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2035 (estimated)
- First posted
- 2 May 2025 (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 explores how adjuvant therapy affects survival in completely resected high-risk stage IA-IB NSCLC patients with different driver gene mutations.
Detailed description
This study aims to evaluate whether tailored, targeted therapy or immunotherapy can effectively prevent cancer recurrence in patients with early-stage (stage IA-IB) non-small cell lung cancer (NSCLC) who have undergone complete surgical resection but are at high risk of recurrence. Based on each patient's specific driver gene mutation status (e.g., EGFR or ALK/ROS1) or wild-type status, participants will receive either targeted therapy or immunotherapy compared to routine follow-up (observation). The goal is to see if these approaches can improve disease-free survival and potentially reduce the risk of lung cancer recurrence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adjuvant therapy | Experimental | Drug: Icotinib, Drug: Rezivertinib, Drug: Ensartinib, Drug: Benmelstobart |
| Observation | No intervention | – |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18-75 years and able to provide written informed consent.
- Primary non-squamous NSCLC confirmed by pathology, with no brain metastases.
- Complete R0 surgical resection (lobectomy, segmentectomy, or pneumonectomy) of stage IA or IB NSCLC (AJCC 8th edition).
- High-risk disease (one or more): low differentiation, solid/micropapillary/complex glandular patterns, vascular invasion, visceral pleural invasion, alveolar space spread, or intermediate/high risk on 14-gene test.
- Documented driver gene status (EGFR mutation, ALK/ROS1 fusion, or wild-type) via postoperative tumor sample.
Key exclusion criteria (11 listed)
- Evidence of unresectable/metastatic NSCLC, incomplete resection (R1/R2), or wedge resection only.
- Prior systemic therapy (e.g., chemotherapy, targeted therapy, immunotherapy) for the current NSCLC.
- Major surgery (excluding lung cancer surgery) within 3 weeks before first study dose.
- Planned concurrent anti-cancer therapy (chemo, radiotherapy, or targeted therapy) during the study.
- Clinically significant cardiac disorders (e.g., poorly controlled hypertension, recent MI or stroke, prolonged QTc).
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 |
|---|---|---|
| IcotinibOral icotinib tablets (125 mg) administered three times daily (TID) for up to 1 year or until disease recurrence or unacceptable toxicity. Icotinib is an EGFR tyrosine kinase inhibitor targeting EGFR-sensitizing mutations. | Drug | Adjuvant therapy |
| RezivertinibOral rezivertinib capsules (100 mg) taken once daily (QD) for up to 1 year or until disease recurrence or unacceptable toxicity. Rezivertinib is an EGFR tyrosine kinase inhibitor targeting EGFR-sensitizing mutations. | Drug | Adjuvant therapy |
| EnsartinibOral ensartinib capsules (225 mg) taken once daily (QD) for up to 1 year or until disease recurrence or unacceptable toxicity. Ensartinib is an ALK/ROS1 tyrosine kinase inhibitor designed to inhibit ALK/ROS1 fusion-driven NSCLC. | Drug | Adjuvant therapy |
| BenmelstobartIntravenous infusion of bemosumab 1200 mg every 3 weeks (Q3W). Treatment continues for up to 4 cycles initially, and may be extended (maintenance) for up to 3 years or until disease recurrence or unacceptable toxicity. Bemosumab is a monoclonal antibody under investigation for immunotherapy in NSCLC. | Drug | Adjuvant therapy |
Primary outcome
Disease-Free Survival (DFS)
Time frame: From randomization until disease recurrence or death (up to approximately 5 years)
Disease-free survival (DFS) is defined as the time from randomization to the first documented disease recurrence (local relapse or distant metastasis confirmed by imaging or pathology) or death from any cause, whichever occurs first. Participants without documented recurrence or death at the time of analysis will be censored at their last disease assessment date.
3 secondary outcomes
Overall Survival (OS)
Time frame: From randomization to death or last follow-up (up to approximately 5 years)
Central Nervous System Disease-Free Survival (CNS DFS)
Time frame: From randomization until CNS progression or death, whichever occurs first (up to approximately 5 years)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: From date of randomization up to approximately 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Icotinib, Rezivertinib and Ensartinib in people with Non-Small Cell Lung Cancer, run by The First Affiliated Hospital of Guangzhou Medical University.
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 9 inclusion and 11 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: opening soon, as of the sponsor's last update on 6 May 2025. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Disease-Free Survival (DFS) (time frame: From randomization until disease recurrence or death (up to approximately 5 years)). 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 6 May 2025.