A Prospective Study of Firmonertinib as First-line Adaptive Therapy Guided by Dynamic ctDNA (MRD) Changes in Locally Advanced or Metastatic EGFR-mutated Non-small Cell Lung Cancer

NCT07661173 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026-LLYJ-0007
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

Exploring the efficacy and safety of adaptively adjusting treatment regimens based on ctDNA (MRD) status for EGFR mutation-positive NSCLC

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  through study completion, an average of 2 years

Secondary Outcomes (4)

• Overall Survival (OS)

  through study completion, an average of 4 years

• Objective Response Rate (ORR)

  through study completion, an average of 2 years

• Disease Control Rate (DCR)

  through study completion, up to 2 years

• Duration of Response (DoR)

  through study completion, an average of 2 years

Study Arms (4)

Arm A1

EXPERIMENTAL

firmonertinib

Drug: Firmonertinib

Arm A2

EXPERIMENTAL

firmonertinib combined with chemotherapy

Drug: Firmonertinib/pemetrexed/Carboplatin

Arm B1

EXPERIMENTAL

firmonertinib combined with chemotherapy

Drug: Firmonertinib/pemetrexed/Carboplatin

Arm B2

EXPERIMENTAL

firmonertinib combined with chemotherapy and antiangiogenic drugs

Drug: Firmonertinib/pemetrexed/Carboplatin/Bevacizumab

Interventions

Firmonertinib DRUG

80mg QD

Arm A1

Firmonertinib/pemetrexed/Carboplatin DRUG

Drug: Firmonertinib daily and pemetrexed plus carboplatin on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by firmonertinib daily with pemetrexed maintenance every 3 weeks.

Arm A2; Arm B1

Firmonertinib/pemetrexed/Carboplatin/Bevacizumab DRUG

Drug: Firmonertinib daily and pemetrexed plus carboplatin on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by firmonertinib daily with pemetrexed and bevacizumab maintenance every 3 weeks.

Arm B2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign a written informed consent before implementing any trial-related procedures;
• At least 18 years of age;
• Have histologically or cytologically confirmed non-squamous non-small cell lung cancer.
• Confirmed presence of EGFR-sensitive mutation-positive by tumor histology, cytology, hematology, or pleural effusion supernatant;
• ECOG score of 0-1;
• According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), there must be at least one measurable lesion on imaging. Lesions located within the previous radiation field that have proven progression can be considered measurable;
• Life expectancy \>3 months at Day 1;
• Patients newly diagnosed with locally advanced (IIIB-IIIC), metastatic, or recurrent (stage IV) lung cancer according to the 9th edition of the TNM classification by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer; not suitable for treatment with surgery or radiotherapy;
• Confirmed presence of EGFR mutation-positive by tumor histology, cytology, or hematology;
• Not previously treated with anti-angiogenic drugs/chemotherapy;
• Brain metastasis patients are allowed to be enrolled, as long as they meet the following conditions:
• Sufficient organ function, and the subjects must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥1.5x10\^9/L without the use of granulocyte colony-stimulating factor in the past 14 days;
• Platelets ≥100×10\^9/L without blood transfusion in the past 14 days;
• Hemoglobin \>9g/dL without blood transfusion or erythropoietin use in the past 14 days;

You may not qualify if:

• The pathology is small cell lung cancer (SCLC), including lung cancer with a mixture of SCLC and non-small cell lung cancer (NSCLC);
• The patient has received the following treatments:
• received systemic anti-tumor therapy within 3 weeks before treatment, such as chemotherapy, targeted therapy, immunotherapy (including Chinese herbal medicine therapy with anti-tumor indications), etc.;
• received any investigational drug therapy within 4 weeks before treatment;
• received high-dose immunosuppressive drugs (systemic glucocorticoids exceeding 10mg/day of prednisone or its equivalent dose) within 4 weeks before treatment;
• received attenuated live vaccines within 4 weeks before treatment (or plans to receive attenuated live vaccines during the study period);
• underwent major surgery (such as thoracotomy, thoracotomy, or Kaifu surgery) within 4 weeks before treatment, or has unhealed surgical wounds, ulcers, or fractures.
• Subjects with clinically uncontrollable pleural/peritoneal effusion (not requiring drainage of effusion or showing no significant increase in effusion after 3 days of cessation of drainage) may be enrolled;
• Subjects with a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonia requiring steroid treatment, or any evidence of clinically active ILD;
• Subjects who have received chest radiotherapy exceeding 30 Gy within 6 months prior to treatment or palliative radiotherapy of 30 Gy or less within 7 days prior to treatment (palliative radiotherapy for bone or intracranial lesions is allowed);
• Subjects who have experienced active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment;
• Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• Subjects who have not fully recovered from toxicity and/or complications caused by any intervention prior to the start of treatment (i.e., grade ≤1 or baseline, excluding fatigue or alopecia);
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive);
• Untreated active hepatitis B (defined as HBsAg positive with HBV-DNA copy number greater than the upper limit of normal in the laboratory department of the research center); Note: Subjects with hepatitis B who meet the following criteria may also be enrolled: 1) HBV viral load \<1000 copies/ml (200 IU/ml) prior to the first dose, and subjects should receive anti-HBV treatment throughout the study drug treatment period to avoid viral reactivation; 2) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV treatment is not required, but close monitoring for viral reactivation is necessary.

Sponsors & Collaborators

• Anhui Provincial Cancer Hospital: lead

Study Sites (1)

Anhui Provincial Cancer Hospital

Hefei, Anhui, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Yueyin Pan

CONTACT

13805695536; panyueyin@ustc.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physicians

Study Record Dates

• First Submitted: April 17, 2026
• First Posted: June 22, 2026
• Study Start: June 6, 2026
• Primary Completion (Estimated): March 6, 2029
• Study Completion (Estimated): May 6, 2031
• Last Updated: June 22, 2026

Record last verified: 2026-04

Locations

CN (1)