Clinical trial NCT06300424: Neoadjuvant Almonertinib Followed by Chemo-immunotherapy in II-IIIB EGFR-mutant NSCLC
Official title: Neoadjuvant Almonertinib Followed by Adebrelimab-based Chemo-immunotherapy in II-IIIB EGFR-mutant Non-small Cell Lung Cancer, a Single Arm, Phase II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
EGFR Gene Mutation
Keywords: non small cell lung cancer
neoadjuvant therapy
immunotherapy
EGFR
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2024-03-08
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II, single-arm, open-label study that assess clinical feasibility and safety of neoadjuvant almonertinib followed by 3 cycles neoadjuvant adebrelimab plus chemotherapy in EGFR-mutant stage IIA-IIIB NSCLC followed by surgery, adjuvant treatment was upon investigators' decisions.

Detailed description: This study plans to include 32 eligible II-IIIB non small cell lung cancer (NSCLC), patients will receive 6 weeks of almonertinib, and to avoid overlap of interstitial lung disease (ILD) and immune-related pneumonitis, 2 weeks of washout period was designed before 3 cycles of adebrelimab + doublet platinum-based chemotherapy is administered. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients with local disease and resectable or potentially resectable NSCLC will receive anatomic resection. Patients who progress upon neoadjuvant treatment and further assessed as 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 undergo optional adjuvant treatment including epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) or immunotherapy upon investigators' consideration or CT surveillance. Patients will be follow-up within 5 years after surgery. The primary endpoint of this study is major pathological response (MPR) defined as no more than 10% residual tumor found in primary lung cancer as per International Association for the Study of Lung Cancer (IASLC) criteria.

Eligibility criteria: Inclusion Criteria:

1. Male or female，Age: 18 Years and older,
2. Subjects voluntarily joined the study and signed informed consent,
3. pathological proven resectable stage II-IIIB non small cell lung cancer (AJCC 8th edition),
4. ECOG PS=0 or 1,
5. resectable or potentially resectable, or resectability discussed by MDT,
6. harboring EGFR mutation: Ex19del, L858R, T790M, G719X, Exon20 insertions, S768I or L861Q
7. measurable lesion as per RECIST1.1.

Exclusion Criteria:

1. pathologica or cytological proven small cell lung cancer, mixed small cell lung cancer or other than non small cell lung cancer,
2. non small cell lung cancer harboring other driver gene alteration with approved targeted drugs,
3. with malignant plural effusion,
4. previous treatment to non small cell lung cancer other than this regimen,
5. received thoracic radiotherapy,
6. currently enrolled in other clinical trial,
7. active or known or suspected autoimmune disease.

Primary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: MPR will be assessed within 2 weeks after surgery
Secondary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: pCR will be assessed within 2 weeks after surgery
measure: Objective Response Rate (ORR)
timeFrame: Tumor response will be evaluated within 2 weeks after almonertinib, and within 3-4 weeks after last dose of neoadjuvant treatment
Other outcomes:
measure: Overall Survival (OS)
timeFrame: up to 60 months.
measure: Event Free Survival (EFS)
timeFrame: From date of initiation of neoadjuvant treatment till the date of first documented disease progression or death, whichever came first, assessed up to 60 months
measure: Incidence of Adverse Events (AEs)
timeFrame: up to 90 days.
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 Provincial People's Hospital
name: Wen-zhao Zhong, PhD
role: PRINCIPAL_INVESTIGATOR
References: