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

NCT ID: NCT07038460

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-31
• Study Completion Date: 2029-12-31

Brief 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. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Group

Group Type: EXPERIMENTAL

Limertinib+sintilimab+chemotherapy

Intervention Type: DRUG

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.

surgery

Intervention Type: PROCEDURE

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).

Osimertinib

Intervention Type: DRUG

Adjuvant treatment with Osimertinib for 2 years

Control Group

Group Type: ACTIVE_COMPARATOR

Limertinib+chemotherapy

Intervention Type: DRUG

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.

surgery

Intervention Type: PROCEDURE

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).

Osimertinib

Intervention Type: DRUG

Adjuvant treatment with Osimertinib for 2 years

Interventions

Limertinib+sintilimab+chemotherapy

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.

Intervention Type: DRUG

Limertinib+chemotherapy

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.

Intervention Type: DRUG

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).

Intervention Type: PROCEDURE

Osimertinib

Adjuvant treatment with Osimertinib for 2 years

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent form

2. Age: 18-75 years.

3. Cytologically/histologically confirmed (via percutaneous lung puncture, bronchoscopy, mediastinoscopy, etc.), previously untreated stage II-IIIB (IASLC 8th Edition Thoracic Tumor Classification) lung adenocarcinoma.

4. Tumor tissue or blood samples confirmed as EGFR-sensitive or rare mutation-positive by laboratory testing

5. Must provide archived tumor tissue or newly resected tumor biopsy samples for PD-L1 IHC testing during screening.

6. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

7. Measurable lesions per RECIST v1.1.

8. Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).

9. 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.

10. 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.

Exclusion Criteria

1. Patients with stage I or IV NSCLC who have previously received systemic anti-tumor therapies (e.g., ICIs, targeted therapy, chemotherapy).

2. Active known or suspected autoimmune diseases (exceptions: type I diabetes, hypothyroidism requiring hormone replacement only, non-progressive skin conditions like vitiligo/psoriasis/alopecia).

3. 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.

4. HIV-positive or AIDS history.

5. Arterial thrombosis within 6 months, or deep vein thrombosis/pulmonary embolism within 3 months.

6. Uncontrolled angina, arrhythmias, or congestive heart failure.

7. Active malignancies within 5 years (except cured cervical/cutaneous carcinoma in situ, superficial bladder/prostate/breast cancer).

8. Contraindications to local therapies (surgery, radiotherapy, or intervention) per investigator judgment.

9. Hypersensitivity to sintilimab, limertinib, chemotherapy agents, or excipients.

10. Unwillingness to sign informed consent or comply with follow-up.

11. Any condition compromising trial integrity or patient safety, as judged by the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wen-zhao ZHONG

OTHER

Sponsor Role: lead

Responsible Party

Wen-zhao ZHONG

Ph.D

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity

Guangzhou, Guangdong, China

Guangdong Province People's Hospital

Guangzhou, Guangdong, China

Sun Yet-Sen University Cancer Center

Guangzhou, Guangdong, China

Hunan Cancer Hospital

Changsha, Hunan, China

Xiangya Hospital Central South University

Changsha, Hunan, China

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Jin Kang

Role: CONTACT

kangjin@gdph.org.cn

020 8382 7812

Facility Contacts

Ming Zhou

Role: primary

020-66673666

Jin Kang

Role: primary

kangjin@gdph.org.cn

Hong Yang

Role: primary

Lin Wu

Role: primary

0731-88651900

Yang Gao

Role: primary

0731-89753999

Fumin Qiu

Role: primary

0571-87783777

Junqiang Fan

Role: backup

Other Identifiers

GuangdongPPHosp

Identifier Type: -

Identifier Source: org_study_id