Afatinib Combined With Chemotherapy as Conversion Therapy in Unresectable EGFR Sensitive Mutation-positive Stage III NSCLC

A Phase II Trial to Evaluate the Efficacy and Safety of Afatinib Combined With Chemotherapy as Conversion Therapy in Unresectable EGFR Sensitive Mutation-positive Stage III Non-small Cell Lung Cancer

This is a phase II, single-arm study to evaluate the efficacy and safety of Afatinib plus chemotherapy as conversion treatment in patients with unresectable EGFR sensitive mutation-positive stage III non-small cell lung cancer.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Afatinib plus chemotherapy as conversion treatment

Detailed Description

This single-arm, open-label, prospective phase II clinical trial was designed to evaluate the efficacy and safety of afatinib plus chemotherapy as conversion treatment in patients with unresectable EGFR sensitive mutation-positive stage III non-small cell lung cancer.

The primary endpoint was the rate of NSCLC converting to resectable tumors. The secondary endpoints included R0 resection rate, major pathological response (MPR) rate, pathological complete response (pCR) rate, tumor downstaging rate, objective response rate (ORR), disease control rate (DCR), 1-year event-free survival (EFS) rate, EFS and overall survival (OS).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hua Zhang, PhD; Phone Number: 0531-83347512; Email: 95192789@qq.com

Study Locations

• China
  • shangdong
    • Jinan, shangdong, China, 250000
      • Recruiting
      • Shandong Public Health Clinical Center
      • Contact: hua zhang; Phone Number: 0531-83347512; Email: 95192789@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically or cytologically confirmed diagnosis of unresectable Stage III non-small cell lung cancer as judged by the investigator.
• Tissue or blood samples tested and confirmed to be positive for EGFR sensitive mutation
• ECOG Performance Status of 0-1
• At least one measurable lesion according to RECIST 1.1
• Adequate organ and marrow function

Exclusion Criteria:

• Histologically or cytologically confirmed combined SCLC and NSCLC, large cell neuroendocrine carcinoma, and sarcoma-like carcinoma
• The presence of malignant pleural effusion
• Prior systemic anti-cancer therapy for non-small cell lung cancer
• Prior local radiotherapy for NSCLC
• Patients with uncontrolled gastrointestinal diseases that may affect the absorption of test drugs (such as Crohn's disease, ulcerative colitis, absorption disorders, or diarrhea of any cause ≥ Grade 2 CTCAE) according to the investigator's assessment

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: Afatinib plus chemotherapy; Patients with unresectable EGFR sensitive mutation-positive stage III NSCLC will receive 3-4 cycles of afatinib plus chemotherapy as the conversion treatment (afatinib 40mg qd; carboplatin (AUC 5) on day 1, and pemetrexed (500 mg/m2 for non-squamous carcinoma) or nab-paclitaxel (260 mg/m2 for squamous carcinoma) d1 q3w), and then surgery will be provided for patients who are suitable for primary tumor resection. Maintenance treatment with afatinib 40mg qd will continue up to 2 years or disease progression after surgery.

Drug: Afatinib plus chemotherapy as conversion treatment; Patients with unresectable EGFR sensitive mutation-positive stage III NSCLC will receive 3-4 cycles of afatinib plus chemotherapy as the conversion treatment, and then surgery will be provided for patients who are suitable for primary tumor resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of NSCLC converting to resectable tumors	The proportion of unresectable NSCLC patients who are converted to being suitable for surgery after 3-4 cycles afatinib plus chemotherapy.	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	The proportion of R0 resection in patients who receive surgery	immediately after the surgery
Major pathologic response (MPR) Rate	The proportion of patients who achieve MRP among those receiving surgery	Up to 12 weeks
Pathologic complete response (pCR) Rate	The proportion of patients who achieve pCR among those receiving surgery	Up to 12 weeks
Tumor downstaging rate	The proportion of patients who reach the successful downstaging criteria for NSCLC	Up to 12 weeks
Objective response rate (ORR)	The proportion of patients who have a complete response (CR) or partial response (PR).	Up to five years
Disease control rate (DCR)	The proportion of patients who have a best overall response of CR, PR, or stable disease (SD).	Up to five years
Event-free survival (EFS)	The length of time after initial administration the patient remains free of recurrence/progression or death, whatever the cause.	Up to five years
The 2-year progression-free survival (PFS) rate	The proportion of patients who are event-free.	Up to two years
Overall Survival (OS)	The length of time after initial administration the patient remains alive	Up to five years

Collaborators and Investigators

• Sponsor: Shandong Public Health Clinical Center
• Investigators: Principal Investigator: Hua Zhang, PhD, Shandong Public Health Clinical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Conversion Therapy; Afatinib
• 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; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: GWLCZXEC2024-56-2

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