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

Neoadjuvant Almonertinib Followed by Adebrelimab-based Chemo-immunotherapy in II-IIIB EGFR-mutant Non-small Cell Lung Cancer, a Single Arm, Phase II Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer; EGFR Gene Mutation
• Intervention / Treatment: Drug: Carboplatin; Drug: almonertinib; Drug: Nab paclitaxel

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Almonertinib and Chemo-immunotherapy; 6 weeks of almonertinib followed by 3 cycles of neoadjuvant adebrelimab (1200mg every 3 weeks) with nab-paclitaxel and carboplatin (nab-paclitaxel 135 mg/m2, d1 and d8, and carboplatin AUC 5, d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including EGFR-TKIs up to 3 years or immunotherapy for up to 1 year or till disease progression or unacceptable toxicity.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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
Incidence of Adverse Events (AEs)	Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment	up to 90 days.

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Principal Investigator: Wen-zhao Zhong, PhD, Guangdong Provincial People'S Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): January 26, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: March 3, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; EGFR; neoadjuvant therapy; non small cell lung cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Coordination Complexes; Health Care Economics and Organizations; Economics; Carboplatin; aumolertinib; Taxes
• Other Study ID Numbers: KY2024-162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No