Ignite Creation Date:
2025-12-25 @ 2:11 AM
Ignite Modification Date:
2026-01-04 @ 9:48 PM
Study NCT ID:
NCT07038460
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-06-26
First Post:
2025-06-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief 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
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'C000596361', 'term': 'osimertinib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 134}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-07', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2029-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-18', 'studyFirstSubmitDate': '2025-06-18', 'studyFirstSubmitQcDate': '2025-06-18', 'lastUpdatePostDateStruct': {'date': '2025-06-26', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-06-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Pathologic Complete Response Rate', 'timeFrame': 'Up to approximately 6 weeks following completion of surgery', 'description': 'Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes.'}], 'secondaryOutcomes': [{'measure': 'Major Pathological Response (mPR) Rat', 'timeFrame': 'Up to approximately 6 weeks following completion of surgery', 'description': 'mPR rate is defined as ≤ 10% residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy.'}, {'measure': 'Event Free Survival (EFS)', 'timeFrame': 'Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline', 'description': 'EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first.'}, {'measure': 'Disease free survival (DFS)', 'timeFrame': 'Up to approximately 2 years following the begining of Post-operative Assessment baseline', 'description': 'DFS is defined as the time from surgery to disease recurrence or death due to any cause.'}, {'measure': 'Overall survival (OS)', 'timeFrame': 'Up to approximately 2.5 years', 'description': 'OS is defined as the time from randomization to death due to any cause.'}, {'measure': 'Objective response rate(ORR)', 'timeFrame': 'Up to approximately 2 weeks before surgery', 'description': '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.'}, {'measure': 'Safety parameters:AE', 'timeFrame': 'Up to approximately 2.5 years', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['NSCLC', 'EGFRmut', 'Limertinib', 'Sintilimab'], 'conditions': ['Resectable Non-small Cell Lung Cancer']}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Signed written informed consent form\n2. Age: 18-75 years.\n3. Cytologically/histologically confirmed (via percutaneous lung puncture, bronchoscopy, mediastinoscopy, etc.), previously untreated stage II-IIIB (IASLC 8th Edition Thoracic Tumor Classification) lung adenocarcinoma.\n4. Tumor tissue or blood samples confirmed as EGFR-sensitive or rare mutation-positive by laboratory testing\n5. Must provide archived tumor tissue or newly resected tumor biopsy samples for PD-L1 IHC testing during screening.\n6. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.\n7. Measurable lesions per RECIST v1.1.\n8. Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).\n9. 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.\n10. 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.\n\nExclusion Criteria:\n\n1. Patients with stage I or IV NSCLC who have previously received systemic anti-tumor therapies (e.g., ICIs, targeted therapy, chemotherapy).\n2. Active known or suspected autoimmune diseases (exceptions: type I diabetes, hypothyroidism requiring hormone replacement only, non-progressive skin conditions like vitiligo/psoriasis/alopecia).\n3. 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.\n4. HIV-positive or AIDS history.\n5. Arterial thrombosis within 6 months, or deep vein thrombosis/pulmonary embolism within 3 months.\n6. Uncontrolled angina, arrhythmias, or congestive heart failure.\n7. Active malignancies within 5 years (except cured cervical/cutaneous carcinoma in situ, superficial bladder/prostate/breast cancer).\n8. Contraindications to local therapies (surgery, radiotherapy, or intervention) per investigator judgment.\n9. Hypersensitivity to sintilimab, limertinib, chemotherapy agents, or excipients.\n10. Unwillingness to sign informed consent or comply with follow-up.\n11. Any condition compromising trial integrity or patient safety, as judged by the investigator.'}, 'identificationModule': {'nctId': 'NCT07038460', 'acronym': 'NEO-LISI', 'briefTitle': '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', 'organization': {'class': 'OTHER', 'fullName': "Guangdong Provincial People's Hospital"}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'GuangdongPPHosp'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Experimental Group', 'interventionNames': ['Drug: Limertinib+sintilimab+chemotherapy', 'Procedure: surgery', 'Drug: Osimertinib']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Control Group', 'interventionNames': ['Drug: Limertinib+chemotherapy', 'Procedure: surgery', 'Drug: Osimertinib']}], 'interventions': [{'name': 'Limertinib+sintilimab+chemotherapy', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Experimental Group']}, {'name': 'Limertinib+chemotherapy', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Control Group']}, {'name': 'surgery', 'type': 'PROCEDURE', 'description': '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).', 'armGroupLabels': ['Control Group', 'Experimental Group']}, {'name': 'Osimertinib', 'type': 'DRUG', 'description': 'Adjuvant treatment with Osimertinib for 2 years', 'armGroupLabels': ['Control Group', 'Experimental Group']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Guangzhou', 'state': 'Guangdong', 'country': 'China', 'contacts': [{'name': 'Ming Zhou', 'role': 'CONTACT', 'phone': '020-66673666'}], 'facility': 'Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity', 'geoPoint': {'lat': 23.11667, 'lon': 113.25}}, {'city': 'Guangzhou', 'state': 'Guangdong', 'country': 'China', 'contacts': [{'name': 'Jin Kang', 'role': 'CONTACT', 'email': 'kangjin@gdph.org.cn'}], 'facility': "Guangdong Province People's Hospital", 'geoPoint': {'lat': 23.11667, 'lon': 113.25}}, {'city': 'Guangzhou', 'state': 'Guangdong', 'country': 'China', 'contacts': [{'name': 'Hong Yang', 'role': 'CONTACT'}], 'facility': 'Sun Yet-Sen University Cancer Center', 'geoPoint': {'lat': 23.11667, 'lon': 113.25}}, {'city': 'Changsha', 'state': 'Hunan', 'country': 'China', 'contacts': [{'name': 'Lin Wu', 'role': 'CONTACT', 'phone': '0731-88651900'}], 'facility': 'Hunan Cancer Hospital', 'geoPoint': {'lat': 28.19874, 'lon': 112.97087}}, {'city': 'Changsha', 'state': 'Hunan', 'country': 'China', 'contacts': [{'name': 'Yang Gao', 'role': 'CONTACT', 'phone': '0731-89753999'}], 'facility': 'Xiangya Hospital Central South University', 'geoPoint': {'lat': 28.19874, 'lon': 112.97087}}, {'city': 'Hangzhou', 'state': 'Zhejiang', 'country': 'China', 'contacts': [{'name': 'Fumin Qiu', 'role': 'CONTACT', 'phone': '0571-87783777'}, {'name': 'Junqiang Fan', 'role': 'CONTACT'}], 'facility': 'The Second Affiliated Hospital Zhejiang University School of Medicine', 'geoPoint': {'lat': 30.29365, 'lon': 120.16142}}], 'centralContacts': [{'name': 'Jin Kang', 'role': 'CONTACT', 'email': 'kangjin@gdph.org.cn', 'phone': '020 8382 7812'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Wen-zhao ZHONG', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Ph.D', 'investigatorFullName': 'Wen-zhao ZHONG', 'investigatorAffiliation': "Guangdong Provincial People's Hospital"}}}}