Neoadjuvant Almonertinib Followed by Chemo-immunotherapy in II-IIIB EGFR-mutant NSCLC

Non Small Cell Lung Cancer Clinical Trial

— NEOVADE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06300424
• Other study ID #: KY2024-162
• Status: Recruiting
• Phase: Phase 2
• Start date: April 2024
• Est. completion date: September 2027

Study information

• Verified date: April 2024
• Source: Guangdong Provincial People's Hospital
• Contact: Wen-zhao Zhong, PhD
• Phone: +862083827812
• Email: syzhongwenzhao[@]scut.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: September 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR Gene Mutation
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• almonertinib
110mg qd
• Carboplatin
AUC 5, d1 every 3 weeks
• Nab paclitaxel
135 mg/m2, d1,d8 every 3 weeks

Locations

Country	Name	City	State
China	Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Provincial People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival (OS)	From date of initiation of neoadjuvant treatment till the date of all-cause death, assessed up to 60 months.	up to 60 months.
Other	Event Free Survival (EFS)	Time from initiation of neoadjuvant treatment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause.	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
Other	Incidence of Adverse Events (AEs)	Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment	up to 90 days.
Primary	Major Pathological Response (MPR)	MPR was defined as percentage of tumor cells within tumor bed less than 10% for primary lung lesions	MPR will be assessed within 2 weeks after surgery
Secondary	Pathological Complete Response (pCR)	The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment.	pCR will be assessed within 2 weeks after surgery
Secondary	Objective Response Rate (ORR)	ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of participants. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.	Tumor response will be evaluated within 2 weeks after almonertinib, and within 3-4 weeks after last dose of neoadjuvant treatment