Neoadjuvant Therapy With Firmonertinib Combined With Anlotinib and Platinum-Based Doublet Chemotherapy for Resectable EGFR-Mutated NSCLC

Firmonertinib Combined With Anlotinib and Platinum-Based Doublet Chemotherapy as Neoadjuvant Therapy in Patients With EGFR-mutant Resectable NSCLC : A Prospective, Multicenter, Single Arm, Phase II Exploratory Clinical Study

Exploring the efficacy and safety of firmonertinib combined with anlotinib and platinum-based doublet chemotherapy as neoadjuvant therapy in patients with EGFR-mutant resectable NSCLC

Study Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Therapy; EGFR; NSCLC (Non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: Firmonertinib combined anlotinib and chemotehrapy

Detailed Description

Multiple ongoing clinical trials are investigating the efficacy and safety of the new generation EGFR-TKI in neoadjuvant therapy. The research on neoadjuvant targeted therapy is still in its early stages, and the optimal treatment time is still unclear. Additional data from ongoing clinical trials will be crucial in determining the optimal duration of neoadjuvant targeted therapy. Compared with neoadjuvant immunotherapy, preliminary data suggest that the MPR or pathological complete response (pCR) rate of neoadjuvant targeted therapy may be lower, while other efficacy endpoints (R0 resection rate, reduction in progression, Event Free Survival (EFS), DFS, PFS) are comparable.

Firmonertinib is a third-generation EGFR-TKI developed by Shanghai Ailisi Pharmaceutical Technology Co., Ltd. It can simultaneously target EGFR sensitive mutations and Thr790Met mutations [37]. FURLONG research has shown that in the first-line treatment of EGFR mutation positive NSCLC patients in China, fumatinib is superior to first generation EGFR-TKI gefitinib in terms of PFS, and patients have better tolerance. This benefit is consistent in most pre-designated subgroups, including patients with central nervous system metastases.

Anlotinib is a small molecule multi-target TKI independently developed by China Zhengda Tianqing Pharmaceutical Group Co., Ltd. It can effectively inhibit kinases such as VEGFR, PDGFR, FGFR, and c-Kit, and has anti-tumor angiogenesis and tumor growth inhibition effects. The oral presentation of the FLALTER study at the 2022 European Society for Medical Oncology (ESMO) annual meeting showed that the combination of anlotinib and gefitinib significantly prolonged the median progression free survival (PFS) of patients with metastatic EGFR mutant NSCLC compared to the gefitinib monotherapy group.

The preliminary results of multiple ongoing clinical trials indicate that the ORR of anlotinib combined with third-generation EGFR-TKI for the treatment of EGFR mutant advanced NSCLC ranges from 65.20% to 96.15%, demonstrating the enormous potential of the combination therapy. The aim of this study is to investigate the efficacy and safety of neoadjuvant firmonertinib combined with anlotinib and chemotherapy in the treatment of resectable EGFR mutation positive NSCLC.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sheng Wang; Phone Number: 15871415599; Email: wangshenghbch@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
      • Contact: Sheng Wang; Phone Number: 15871415599

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. EGFR mutation positive non-small cell lung cancer (including 19Del and 21L858R) confirmed by biopsy
2. Resectable stage IIA-IIIB (8th edition TNM staging) non-small cell lung cancer diagnosed by chest CT, PET-CT, or/and EBUS
3. No systemic metastasis (head MRI, whole-body bone scan PET-CT、 Liver and adrenal CT scans, etc
4. Good lung function, able to tolerate surgical treatment
5. Age 18 and above
6. At least one measurable tumor lesion (with a maximum diameter of 10mm or more as measured by CT)
7. Other major organs (liver, kidney, blood system, etc.) are functioning normally:

1）Hemoglobin ≥ 9.0 g/dL (or can be maintained through blood transfusion or exceed this standard) 2）Red blood cell count ≥ 2.0 × 10^9/L 3）Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L 4）Platelet count ≥ 100 × 10^9/L 5）Total bilirubin is within the normal range 6）Alanine transaminase, aspartate transaminase, and alkaline phosphatase ≤ 2.5 times the upper limit of normal values 7）Creatinine ≤ 2.0 mg/dL; Creatinine clearance rate ≥ 60ml/min 8）The international normalized ratio (INR) of prothrombin time to activated partial thromboplastin time for patients who have not received anticoagulant therapy is ≤ 1.5 times the upper limit of normal. Patients who have received comprehensive or intravenous anticoagulant therapy can only participate in clinical trials if the dosage of anticoagulant drugs is stable for more than 2 weeks and the coagulation test results are within the local treatment range.

8. ECOG PS score is 0-1 9. Women of childbearing age must undergo a pregnancy test within 7 days before treatment, and the result is negative. During the trial period and within 30 days after the end of the trial, reliable contraceptive measures such as intrauterine devices, birth control pills, condoms, etc. should be taken. During the trial period and within 30 days after the end of the trial, men of childbearing age should use condoms for contraception; 10. Patients should sign an informed consent form

Exclusion Criteria:

1. The patient has received systemic anti-cancer treatment for non-small cell lung cancer, including surgical treatment, local radiotherapy, cytotoxic drug therapy, targeted drug therapy, etc
2. Patients with other cancers (excluding cervical cancer in situ, cured basal cell carcinoma, and bladder epithelial tumors [including Ta and Tis]) within the 5 years prior to the trial, unless they have small cell lung cancer
3. The patient has any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, angina that has started to occur in the past 3 months, congestive heart failure [≥ NYHA Grade II], myocardial infarction (6 months prior to enrollment), severe arrhythmia, and liver, kidney, or metabolic diseases that require medication treatment)
4. The patient is an active hepatitis B, hepatitis C or HIV carrier
5. Severe or newly diagnosed gastrointestinal disease patients with diarrhea as the main symptom
6. The patient is receiving treatment with P-glycoprotein inhibitors
7. Individuals who have previously suffered or are currently suffering from cardiovascular malformations
8. The patient has previously suffered from or is currently suffering from interstitial lung disease
9. The patient has undergone other major systemic surgeries or suffered severe trauma within the 3 months prior to the trial
10. Suffering from neurological or psychiatric disorders
11. The patient has malabsorption
12. Female patients in pregnancy or lactation period
13. Other researchers believe that patients are not suitable for inclusion in the study

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: Experimental Group; Firmonertinib combined with anlotinib and chemotherapy	Drug: Firmonertinib combined anlotinib and chemotehrapy; EGFR-TKI: Firmonertinib 80mg daily Antiangiogenic drugs: Anlotinib 8-12mg daily, D1-14 and of 21-day cycles Chemotherapy: pemetrexed plus carboplatin on Day 1 and of 21-day cycles (every 3 weeks) for 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR rate	The proportion of patients with ≤10% residual viable tumor cells in the primary tumor, as assessed by histopathological examination of the resected surgical specimen.	At the time of definitive surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete resection rate (R0 resection)	The proportion of patients who achieve a complete (R0) resection of all known disease, as determined by the surgeon and pathologist at the time of definitive surgical resection.	At the time of definitive surgery
pCR rate	The proportion of patients with no residual invasive tumor in the primary tumor and all sampled lymph nodes, as assessed by histopathological examination of the resected surgical specimen.	At the time of definitive surgery
Event-Free Survival (EFS)	Patients alive and free from disease recurrence, progression, or death from any cause after study enrollment	Through study completion, an average of 4 years
Overall Survival (OS)	Patients alive after study enrollment	Through study completion, an average of 4 years
AE	The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-related adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From the first dose of study treatment up to 30 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: Hubei Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 21, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 21, 2026
• First Submitted That Met QC Criteria: September 3, 2026
• First Posted (Actual): September 8, 2026

Study Record Updates

• Last Update Posted (Actual): September 8, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• 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
• Other Study ID Numbers: LCKY2026007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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