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

NCT07038460 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: GuangdongPPHosp
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 6

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

Keywords

NSCLC; EGFRmut; Limertinib; Sintilimab

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate

  Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes.

  Up to approximately 6 weeks following completion of surgery

Secondary Outcomes (6)

• Major Pathological Response (mPR) Rat

  Up to approximately 6 weeks following completion of surgery

• Event Free Survival (EFS)

  Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline

• Disease free survival (DFS)

  Up to approximately 2 years following the begining of Post-operative Assessment baseline

• Overall survival (OS)

  Up to approximately 2.5 years

• Objective response rate(ORR)

  Up to approximately 2 weeks before surgery

Study Arms (2)

Experimental Group

EXPERIMENTAL

Drug: Limertinib+sintilimab+chemotherapy; Procedure: surgery; Drug: Osimertinib

Control Group

ACTIVE COMPARATOR

Drug: Limertinib+chemotherapy; Procedure: surgery; Drug: Osimertinib

Interventions

Limertinib+sintilimab+chemotherapy 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.

Experimental Group

Limertinib+chemotherapy 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.

Control Group

surgery 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).

Control Group; Experimental Group

Osimertinib DRUG

Adjuvant treatment with Osimertinib for 2 years

Control Group; Experimental Group

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Wen-zhao ZHONG: lead

Study Sites (6)

Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity

Guangzhou, Guangdong, China

Location

Guangdong Province People's Hospital

Guangzhou, Guangdong, China

Location

Sun Yet-Sen University Cancer Center

Guangzhou, Guangdong, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, China

Location

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

MeSH Terms

Interventions

Surgical Procedures, Operative; osimertinib

Central Study Contacts

Jin Kang

CONTACT

020 8382 7812; kangjin@gdph.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ph.D

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: June 26, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

CN (6)