Clinical trial NCT05244213: Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC
Official title: Neoadjuvant Sintilimab Plus Chemotherapy in EGFR-mutant Stage II-IIIB NSCLC: A Single-arm, Open-label Prospective Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
EGFR Activating Mutation
Keywords: Neoadjuvant immunotherapy
Non-small cell lung cancer
EGFR mutation
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2022-02-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A Simon two-stage design was applied. Primary endpoint for this study was MPR. The unacceptable response rate for MPR was less than 10% and desirable response rate was 30%. The error rate for alpha was set as 0.05 and 0.1 for beta. The Optimal assay was chosen and at least 35 patients should be enrolled to meet adequate statical power. 18 patients would be enrolled in stage I and at least 2 patient achieved MPR were required to proceed stage II enrollment. Overall, if 6 achieved MPR out of 35 patients, the study would be determined as positive.
Primary purpose: TREATMENT

Brief summary: Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Sintilimab plus chemotherapy in EGFR-mutant stage IIB-IIIB NSCLC (excluding N3) followed by optional adjuvant treatment upon investigators' decisions.

Detailed description: 35 eligible patients will be enrolled and 3 cycles of Sintilimab 200mg + doublet platinum-based chemotherapy will be administered. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including EGFR-TKI upon investigators' consideration. Patients will be followed with 5 years after surgery. The primary objective of the study is major pathological response (MPR) defined as no more than 10% residual tumor found in primary lung cancer.

Eligibility criteria: Inclusion Criteria:

1. Age :18 Years to 75 Years;
2. ECOG physical score 0-1 points; expected survival time ≥ 3 months;
3. Pathologically confirmed diagnosis with Stage II-IIIB(N2) NSCLC which harbored sensitive and rare EGFR alteration. Suspected N2 disease should be confirmed by either mediastinoscopy or EBUS. N1 disease could be determined through PET/CT but biopsy of primary lung cancer is needed;
4. At least one measurable target lesion according to the RECIST 1.1 standard;
5. The main organ function meets the following criteria: 1) blood routine: absolute value of neutrophils ≥ 1.5 × 109 / L, platelets ≥ 75 × 109 / L, hemoglobin ≥ 80 g / L; 2) blood biochemistry: total bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal value (if liver metastasis, ≤ upper limit of normal value 5 times), serum creatinine ≤ 1.5 times the upper limit of normal;
6. Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

Exclusion Criteria:

1. Stage I and stage IV NSCLC;
2. Large panel NGS indicated ALK fusion or any other driver mutations;
3. Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
4. Patients who have previously used any other anti-tumor drugs or radiotherapy;
5. A history of active bleeding within the 6 months before enrollment, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;
6. Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections;
7. Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
8. Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
9. Patients with low compliance or willingness to take the drugs and surveillance.

Primary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: MPR will be assessed within 2 weeks after surgery
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Tumor response will be evaluated within 3-4 weeks after last dose of neoadjuvant treatment
measure: Pathological Complete Response (pCR)
timeFrame: pCR will be assessed within 2 weeks after surgery
measure: Progression-free Survival (PFS)
timeFrame: From date of initiation of neoadjuvant treatment till the date of first documented disease progression or death, whichever came first, assessed up to 36 months.
measure: Overall Survival (OS)
timeFrame: From date of initiation of neoadjuvant treatment till the date of all-cause death, assessed up to 60 months.
measure: Adverse Events (AEs)
timeFrame: From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
state: Guangdong
Study officials:
affiliation: Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital
name: Wen-zhao Zhong, PhD
role: PRINCIPAL_INVESTIGATOR
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