A Phase II Single-Center Exploratory Study on the Efficacy and Safety of Neoadjuvant Chemotherapy Sequentially Combined with Sintilimab in Resectable EGFR-Mutant Stage II-IIIB Non-Squamous Non-Small Cell Lung Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Pemetrexed 500 mg/m2
- Conditions
- Lung Cancer
- Sponsor
- Shanghai Chest Hospital
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- major pathological response (MPR)
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is a prospective, single-arm, single-center Phase II trial, aiming to investigate efficacy and safety of neoadjuvant chemotherapy sequentially combined with sintilimab in resectable EGFR-mutant stage II-IIIB non-squamous NSCLC patients
Detailed Description
Previous studies have confirmed the efficacy of neoadjuvant chemotherapy and immunotherapy in NSCLC patients without driver gene mutations, while their effectiveness in patients with driver gene mutations remains controversial. This study is a prospective, single-arm, single-center Phase II trial targeting eligible subjects with resectable EGFR-mutated stage II-IIIB non-squamous non-small cell lung cancer, aiming to evaluate the efficacy and safety of sintilimab combined with chemotherapy as neoadjuvant therapy. Eligible subjects who meet the inclusion criteria and have signed the informed consent will receive sintilimab in combination with chemotherapy, with a treatment cycle of 3 weeks. A tumor assessment will be conducted before the start of the third cycle of treatment, and surgery will be performed within 3-6 weeks after the last cycle of neoadjuvant therapy, with a tumor assessment conducted 7 days prior to surgery. After completing local treatment (surgery), researchers will offer optional adjuvant therapy to patients, including EGFR-TKI. Concurrently, dynamic blood samples will be collected before neoadjuvant therapy and after each treatment cycle for exploratory analysis, with the evaluation of MPR and pCR based on circulating tumor DNA minimal residual disease (ctDNA-MRD).
Investigators
Hua Zhong
Dr.
Shanghai Chest Hospital
Eligibility Criteria
Inclusion Criteria
- •Sign a written informed consent prior to any study-related procedures;
- •Be aged ≥18 years;
- •Have a histopathologically confirmed diagnosis of stage II-IIIB (N2) non-squamous NSCLC, as per the9th edition TNM staging system by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer, with suspected N2 disease confirmed via mediastinoscopy or EBUS;
- •Have histologically, cytologically, or hematologically confirmed presence of EGFR-sensitive mutations (Ex19del, L858R), with co-existing driver mutations allowed;
- •Have sufficient tissue samples for PD-L1 immunohistochemistry and NGS mutation testing; if tissue samples are inadequate, consent to undergo blood NGS testing;
- •PD-L1 expression level ≥1%;
- •Have at least one radiologically measurable lesion as per the RECIST criteria version1.1;
- •Be assessed by a surgeon as having pulmonary or other organ function sufficient to tolerate local surgical treatment;
- •Have no prior history of anti-tumor treatment;
- •Have an ECOG performance status of0-1;
Exclusion Criteria
- •Pathology of small cell lung cancer (SCLC), including mixed SCLC and NSCLC;
- •Stage I and IV NSCLC, patients who have previously received systemic antitumor treatments such as immunotherapy, targeted therapy, or chemotherapy;
- •Stage III unresectable NSCLC patients;
- •Patients with rare EGFR mutations;
- •Diagnosis of any malignancy other than NSCLC within5 years prior to the first dose, excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has been surgically cured;
- •Currently participating in an interventional clinical study or having received other investigational drugs or device therapies within4 weeks prior to the first dose;
- •Use of traditional Chinese medicine or immunomodulatory drugs with indications for NSCLC within2 weeks prior to the first dose (including thymosin, interferon, interleukin, except for local use to control pleural effusion);
- •Active autoimmune disease requiring systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressants) within2 years prior to the first dose; replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic treatment;
- •Systemic corticosteroid therapy (excluding nasal, inhaled, or other local routes of corticosteroid administration) or any other form of immunosuppressive therapy within7 days prior to the first dose; Note: Physiological doses of corticosteroids (≤10 mg/day of prednisone or equivalent) are permitted;
- •Clinically uncontrollable pleural effusion/ascites (subjects who do not require drainage or whose effusion does not significantly increase after stopping drainage for3 days may be enrolled);
Arms & Interventions
Arm 1
Resectable EGFR-Mutant Stage II-IIIB Non-Squamous Non-Small Cell Lung Cancer Patients. Eligible subjects who meet the inclusion criteria and have signed the informed consent will receive sintilimab in combination with chemotherapy, with a treatment cycle of 3 weeks. A tumor assessment will be conducted before the start of the third cycle of treatment, and surgery will be performed within 3-6 weeks after the last cycle of neoadjuvant therapy, with a tumor assessment conducted 7 days prior to surgery. After completing local treatment (surgery), researchers will offer optional adjuvant therapy to patients, including EGFR-TKI.
Intervention: Pemetrexed 500 mg/m2
Arm 1
Resectable EGFR-Mutant Stage II-IIIB Non-Squamous Non-Small Cell Lung Cancer Patients. Eligible subjects who meet the inclusion criteria and have signed the informed consent will receive sintilimab in combination with chemotherapy, with a treatment cycle of 3 weeks. A tumor assessment will be conducted before the start of the third cycle of treatment, and surgery will be performed within 3-6 weeks after the last cycle of neoadjuvant therapy, with a tumor assessment conducted 7 days prior to surgery. After completing local treatment (surgery), researchers will offer optional adjuvant therapy to patients, including EGFR-TKI.
Intervention: carboplatin
Arm 1
Resectable EGFR-Mutant Stage II-IIIB Non-Squamous Non-Small Cell Lung Cancer Patients. Eligible subjects who meet the inclusion criteria and have signed the informed consent will receive sintilimab in combination with chemotherapy, with a treatment cycle of 3 weeks. A tumor assessment will be conducted before the start of the third cycle of treatment, and surgery will be performed within 3-6 weeks after the last cycle of neoadjuvant therapy, with a tumor assessment conducted 7 days prior to surgery. After completing local treatment (surgery), researchers will offer optional adjuvant therapy to patients, including EGFR-TKI.
Intervention: Sintilimab
Outcomes
Primary Outcomes
major pathological response (MPR)
Time Frame: Evaluated within 2 weeks post-surgery.
MPR is defined as ≤10% residual viable tumor cells in the lung and lymph nodes, to be evaluated within 2 weeks post-surgery.
Secondary Outcomes
- Pathological Complete Response (pCR)(Evaluated within 2 weeks post-surgery.)
- Event-Free Survival (EFS)(up to 3 years after enrollment)