Resectable Non-small Cell Lung CancerPhase 2NEO-LISINCT07038460
A Multicenter Phase II Randomized Trial of Limertinib Followed by Sintilimab and Chemotherapy vs. Limertinib Followed by Limertinib and Chemotherapy as Neoadjuvant Therapy in Resectable Stage II-IIIB EGFR-Mutant NSCLC
A Phase 2 study testing Limertinib+sintilimab+chemotherapy, Limertinib+chemotherapy and surgery in people with Resectable Non-small Cell Lung Cancer, run by Wen-zhao ZHONG at 6 sites in China.
Trial summary
This clinical trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Limertinib Followed by Sintilimab and Chemotherapy in resectable Stage II-IIIB EGFR-Mutant NSCLC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Resectable Non-small Cell Lung Cancer
- What is being tested?
- Limertinib+sintilimab+chemotherapy, Limertinib+chemotherapy and surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 6 sitesChina
- Study dates
- Jul 2025to Dec 2029
- Phase
- Phase 2
- 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
- Signed written informed consent form
- Age: 18-75 years.
- Cytologically/histologically confirmed (via percutaneous lung puncture, bronchoscopy, mediastinoscopy, etc.), previously untreated stage II-IIIB (IASLC 8th Edition Thoracic Tumor Classification) lung adenocarcinoma.
- Tumor tissue or blood samples confirmed as EGFR-sensitive or rare mutation-positive by laboratory testing
- Must provide archived tumor tissue or newly resected tumor biopsy samples for PD-L1 IHC testing during screening.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
Show all 10Show fewer
- Measurable lesions per RECIST v1.1.
- Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).
- Adequate organ and bone marrow function (within 7 days prior to enrollment; no corrective therapies within 14 days prior to testing): • Hematology: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥100 g/L. • Hepatic: Total bilirubin ≤1.5×ULN; AST/ALT ≤2.5×ULN; albumin ≥35 g/L. • Renal: Serum creatinine ≤1.5×ULN; CrCl ≥60 mL/min (Cockcroft-Gault formula); urine protein <2+ or 24-hour urine protein <1 g. Cockcroft-Gault formula: • Female: CrCl = [(140 - age) × weight (kg) × 0.85] / [72 × serum creatinine (mg/dL)]. • Male: CrCl = [(140 - age) × weight (kg)] / [72 × serum creatinine (mg/dL)]. • Coagulation: INR ≤1.5×ULN; PT/APTT ≤1.5×ULN.
- For women of childbearing potential: Negative urine/serum pregnancy test within 7 days prior to first dose. Confirmatory blood test required if urine test is positive.
Who cannot join
- Patients with stage I or IV NSCLC who have previously received systemic anti-tumor therapies (e.g., ICIs, targeted therapy, chemotherapy).
- Active known or suspected autoimmune diseases (exceptions: type I diabetes, hypothyroidism requiring hormone replacement only, non-progressive skin conditions like vitiligo/psoriasis/alopecia).
- Active hepatitis B (HBsAg-positive) or hepatitis C (HCV RNA-positive). Patients with resolved HBV infection (HBsAg-negative, HBcAb-positive) must provide HBV DNA-negative results. HCV antibody-positive patients require negative HCV RNA PCR.
- HIV-positive or AIDS history.
- Arterial thrombosis within 6 months, or deep vein thrombosis/pulmonary embolism within 3 months.
- Uncontrolled angina, arrhythmias, or congestive heart failure.
Show all 11Show fewer
- Active malignancies within 5 years (except cured cervical/cutaneous carcinoma in situ, superficial bladder/prostate/breast cancer).
- Contraindications to local therapies (surgery, radiotherapy, or intervention) per investigator judgment.
- Hypersensitivity to sintilimab, limertinib, chemotherapy agents, or excipients.
- Unwillingness to sign informed consent or comply with follow-up.
- Any condition compromising trial integrity or patient safety, as judged by the investigator.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
China6 sites
Hunan Cancer Hospital
Changsha, Hunan
Lin Wu, 0731-88651900
Xiangya Hospital Central South University
Changsha, Hunan
Yang Gao, 0731-89753999
Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity
Guangzhou, Guangdong
Ming Zhou, 020-66673666
Guangdong Province People's Hospital
Guangzhou, Guangdong
Jin Kang, kangjin@gdph.org.cn
Sun Yet-Sen University Cancer Center
Guangzhou, Guangdong
Hong Yang
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang
Fumin Qiu, 0571-87783777
Junqiang Fan
About this study
This clinical trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Limertinib Followed by Sintilimab and Chemotherapy in resectable Stage II-IIIB EGFR-Mutant NSCLC. Untreated stage II-IIIB NSCLC (AJCC 8th edition) patients assessed as surgically resectable by investigators will be randomized 1:1 into the experimental or control group after signing informed consent and meeting eligibility criteria. All patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, experimental group patients discontinue therapy for 1 week, then receive Sintilimab + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles; control group patients receive Limertinib for 9 weeks and Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles. Preoperative tumor assessment is required. Surgery will be performed 2-6 weeks (±7 days) after the first dose of the final cycle. Then patients will recieve 2-year adjuvant Osimertinib starting 1 month post-surgery. If imaging assessment after 6 weeks of limertinib treatment shows lesion enlargement but remains confined to stage II-IIIB, the investigator will decide whether the patient continues study treatment or not; if progression occurs to unresectable stage III or advanced disease, the patient must discontinue. The primary endpoint is pathological complete response (pCR) rate.
- Conditions
- Resectable Non-small Cell Lung Cancer
- Being tested
- Limertinib+sintilimab+chemotherapy, Limertinib+chemotherapy, surgery, Osimertinib
- Keywords
- NSCLC, EGFRmut, Limertinib, Sintilimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Limertinib+sintilimab+chemotherapyDrug
Experimental group patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, experimental group patients discontinue therapy for 1 week, then receive Sintilimab + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles.
Limertinib+chemotherapyDrug
Control group group patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, control group patients receive Lilotinib for next 9 weeks + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles.
surgeryProcedure or surgery
The surgical procedure may involve minimally invasive surgery (video-assisted thoracoscopic surgery, robot-assisted surgery) or open thoracotomy. The surgical methods include lobectomy, combined lobectomy, pneumonectomy, sleeve resection, and ipsilateral systematic mediastinal lymph node dissection (for left-sided tumors, stations 4L, 5, 6, 7, and 9 should be included; for right-sided tumors, at least stations 2R, 3A, 4R, 7, and 9 should be included).
OsimertinibDrug
Adjuvant treatment with Osimertinib for 2 years
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Not described Receives: Drug: Limertinib+sintilimab+chemotherapy; Procedure: surgery; Drug: Osimertinib |
| Control Group | Active comparator | Not described Receives: Drug: Limertinib+chemotherapy; Procedure: surgery; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response Rate
Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes.
Measured: Up to approximately 6 weeks following completion of surgery
Secondary outcomes (6)
Major Pathological Response (mPR) Rat
mPR rate is defined as ≤ 10% residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy.
Measured: Up to approximately 6 weeks following completion of surgery
Event Free Survival (EFS)
EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first.
Measured: Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline
Disease free survival (DFS)
DFS is defined as the time from surgery to disease recurrence or death due to any cause.
Measured: Up to approximately 2 years following the begining of Post-operative Assessment baseline
Overall survival (OS)
OS is defined as the time from randomization to death due to any cause.
Measured: Up to approximately 2.5 years
Objective response rate(ORR)
The proportion of patients in whom tumor volume reduction reached the predetermined criteria and was maintained for the minimum required duration is the sum of the complete response (CR) and partial response (PR) rates.
Measured: Up to approximately 2 weeks before surgery
Safety parameters:AE
The relationship of study drug and the severity of all adverse events (AEs), treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), immune-related adverse events (irAEs), serious adverse events (SAEs), infusion-related reactions (IRRs) and surgery delay rate.
Measured: Up to approximately 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2025
- Study startJul 2025 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Resectable 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wen-zhao ZHONG
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Wen-zhao ZHONG, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07038460
- Sponsor's protocol ID
- GuangdongPPHosp
- Acronym
- NEO-LISI
- Status last verified
- Jun 2025
- First submitted
- 18 Jun 2025
- Last updated
- 26 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Randomized Trial of Limertinib Followed by Sintilimab and Chemotherapy vs. Limertinib Followed by Limertinib and Chemotherapy as Neoadjuvant Therapy in Resectable Stage II-IIIB EGFR-Mutant NSCLC
- ClinicalTrials.gov ID
- NCT07038460
- Acronym / sponsor ID
- NEO-LISI / GuangdongPPHosp
- Conditions
- Resectable Non-small Cell Lung Cancer
- Keywords
- NSCLC, EGFRmut, Limertinib, Sintilimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 134 participants (estimated)
- Lead sponsor
- Wen-zhao ZHONGUniversity, hospital or other
- Study start
- Jul 2025 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 26 Jun 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 clinical trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Limertinib Followed by Sintilimab and Chemotherapy in resectable Stage II-IIIB EGFR-Mutant NSCLC. Untreated stage II-IIIB NSCLC (AJCC 8th edition) patients assessed as surgically resectable by investigators will be randomized 1:1 into the experimental or control group after signing informed consent and meeting eligibility criteria. All patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, experimental group patients discontinue therapy for 1 week, then receive Sintilimab + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles; control group patients receive Limertinib for 9 weeks and Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles. Preoperative tumor assessment is required. Surgery will be performed 2-6 weeks (±7 days) after the first dose of the final cycle. Then patients will recieve 2-year adjuvant Osimertinib starting 1 month post-surgery. If imaging assessment after 6 weeks of limertinib treatment shows lesion enlargement but remains confined to stage II-IIIB, the investigator will decide whether the patient continues study treatment or not; if progression occurs to unresectable stage III or advanced disease, the patient must discontinue. The primary endpoint is pathological complete response (pCR) rate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Drug: Limertinib+sintilimab+chemotherapy, Procedure: surgery, Drug: Osimertinib |
| Control Group | Active comparator | Drug: Limertinib+chemotherapy, Procedure: surgery, Drug: Osimertinib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed written informed consent form
- Age: 18-75 years.
- Cytologically/histologically confirmed (via percutaneous lung puncture, bronchoscopy, mediastinoscopy, etc.), previously untreated stage II-IIIB (IASLC 8th Edition Thoracic Tumor Classification) lung adenocarcinoma.
- Tumor tissue or blood samples confirmed as EGFR-sensitive or rare mutation-positive by laboratory testing
- Must provide archived tumor tissue or newly resected tumor biopsy samples for PD-L1 IHC testing during screening.
Key exclusion criteria (11 listed)
- Patients with stage I or IV NSCLC who have previously received systemic anti-tumor therapies (e.g., ICIs, targeted therapy, chemotherapy).
- Active known or suspected autoimmune diseases (exceptions: type I diabetes, hypothyroidism requiring hormone replacement only, non-progressive skin conditions like vitiligo/psoriasis/alopecia).
- Active hepatitis B (HBsAg-positive) or hepatitis C (HCV RNA-positive). Patients with resolved HBV infection (HBsAg-negative, HBcAb-positive) must provide HBV DNA-negative results. HCV antibody-positive patients require negative HCV RNA PCR.
- HIV-positive or AIDS history.
- Arterial thrombosis within 6 months, or deep vein thrombosis/pulmonary embolism within 3 months.
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 |
|---|---|---|
| Limertinib+sintilimab+chemotherapyExperimental group patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, experimental group patients discontinue therapy for 1 week, then receive Sintilimab + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles. | Drug | Experimental Group |
| Limertinib+chemotherapyControl group group patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, control group patients receive Lilotinib for next 9 weeks + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles. | Drug | Control Group |
| surgeryThe surgical procedure may involve minimally invasive surgery (video-assisted thoracoscopic surgery, robot-assisted surgery) or open thoracotomy. The surgical methods include lobectomy, combined lobectomy, pneumonectomy, sleeve resection, and ipsilateral systematic mediastinal lymph node dissection (for left-sided tumors, stations 4L, 5, 6, 7, and 9 should be included; for right-sided tumors, at least stations 2R, 3A, 4R, 7, and 9 should be included). | Procedure or surgery | Control Group, Experimental Group |
| OsimertinibAdjuvant treatment with Osimertinib for 2 years | Drug | Control Group, Experimental Group |
Primary outcome
Pathologic Complete Response Rate
Time frame: Up to approximately 6 weeks following completion of surgery
Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes.
6 secondary outcomes
Major Pathological Response (mPR) Rat
Time frame: Up to approximately 6 weeks following completion of surgery
Event Free Survival (EFS)
Time frame: Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline
Disease free survival (DFS)
Time frame: Up to approximately 2 years following the begining of Post-operative Assessment baseline
Overall survival (OS)
Time frame: Up to approximately 2.5 years
Objective response rate(ORR)
Time frame: Up to approximately 2 weeks before surgery
Safety parameters:AE
Time frame: Up to approximately 2.5 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 26 Jun 2025.
Related trials for Resectable Non-small Cell Lung Cancer
RecruitingPhase 2
Adaptive Chemotherapy for Pd-l1 High REsEctablE NSCLC: A Chemo-PHREE Trial
Nsclc, NSCLC Stage II
RecruitingPhase 1
Propranolol Hydrochloride Combined With Toripalimab and Platinum-based Chemotherapy in Resectable Non-Small Cell Lung Cancer
Resectable Non-Small-Cell Lung Cancer
Active, not recruitingPhase 2
An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer
Resectable Stage IIA to IIIB Non-small Cell Lung Cancer
Recruiting
Prehabilitation Physical Therapy and Relaxation Intervention Program to Promote Resiliency and Operative Success Among Adults Receiving Lung Cancer Surgery, ROAR-LCS Trial
Resectable Lung Non-Small Cell Carcinoma
RecruitingPhase 2
Proton Beam Radiation Therapy After Treatment for Resected N2 Non-Small Cell Lung Cancer
Resectable Lung Non-Small Cell Carcinoma
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.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Limertinib+sintilimab+chemotherapy, Limertinib+chemotherapy and surgery in people with Resectable Non-small Cell Lung Cancer, run by Wen-zhao ZHONG at 6 sites 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 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 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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?
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?
Contact Jin Kang (020 8382 7812, kangjin@gdph.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Complete Response Rate (time frame: Up to approximately 6 weeks following completion of surgery). 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 26 Jun 2025; AzTrials last refreshed its copy on 6 Nov 2026.