Andamertinib, alone or with platinum-doublet chemotherapy, versus platinum-doublet chemotherapy for non-squamous NSCLC with atypical EGFR mutations

An Open-label, Randomized, Multicenter Phase II/III Study to Evaluate the Efficacy and Safety of Andamertinib With or Without Platinum-doublet Chemotherapy Versus Platinum-doublet Chemotherapy in Patients With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Harboring Atypical EGFR Mutations Who Have Not Received Prior Systematic Therapy

This trial tests whether the targeted pill andamertinib, given alone or with platinum-doublet chemotherapy, helps people with untreated advanced non-squamous NSCLC that has atypical EGFR mutations respond better or live longer than standard platinum-doublet chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Avistone Biotechnology Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, radiation, Andamertinib
• Locations: 1 site (Guangzhou)
• Trial ID: NCT07336732 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized, multicenter phase II/III study with a dose-exploration phase followed by a pivotal phase comparing andamertinib (with or without platinum-doublet chemotherapy) against standard platinum-doublet chemotherapy in previously untreated locally advanced or metastatic non-squamous NSCLC with confirmed atypical EGFR mutations. Participants undergo a screening period, receive assigned treatment until discontinuation, and then enter safety and survival follow-up. Key eligibility includes age ≥18, ECOG 0-1, at least one measurable lesion, adequate organ function, and no prior systemic therapy for advanced disease. The trial will collect safety, tolerability, and efficacy outcomes to determine whether andamertinib regimens offer benefit over chemotherapy.

Who should consider this trial

Good fit: Adults (≥18) with unresectable locally advanced or metastatic non-squamous NSCLC, a confirmed atypical EGFR mutation, no prior systemic therapy for advanced disease, ECOG performance status 0–1, and at least one measurable lesion are the intended participants.

Not a fit: Patients with squamous-cell histology, common EGFR mutations rather than atypical variants, prior systemic therapy for advanced disease, poor performance status, inadequate organ function, pregnancy/breastfeeding, or inability to attend the study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could provide a more effective and potentially better-tolerated targeted treatment option for patients with atypical EGFR-mutant non-squamous NSCLC.

How similar studies have performed: While EGFR-targeted drugs have shown clear benefit for common EGFR mutations, evidence for atypical EGFR mutations is limited, so this targeted approach is relatively novel with only limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years at the time of ICF signing.
2. Histologically or cytologically confirmed, unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) non-squamous non-small cell lung cancer (NSCLC).
3. Confirmed EGFR atypical mutation.
4. No prior systemic therapy for locally advanced or metastatic NSCLC.
5. At least one measurable lesion as defined by RECIST v1.1.
6. ECOG PS ≤1.
7. Life expectancy≥12 weeks.
8. Adequate organ function confirmed within 7 days prior to the first dose of study treatment
9. Female participants must use adequate contraceptive measures during study participation and for 90 days after the last dose of study treatment and must not be breastfeeding; female subjects not of childbearing potential must meet at least one of the following criteria at screening: Postmenopausal status; Documentation of irreversible surgical sterilization.
10. Non-sterilized males: Abstinence or contraception use; No sperm donation.
11. Willing and able to provide signed ICF and to comply with all requirements and restrictions listed in the ICF and this study protocol.

Exclusion Criteria:

1. Presence of specific genetic alterations for which approved targeted therapies are available.
2. Recent participation (within 28 days) in another interventional clinical trial.
3. Major surgery within 28 days prior to study entry or planned during the study period.
4. Recent use of anti-tumor traditional proprietary medicine or local anti-tumor therapy.
5. Need for specific concomitant medications (e.g., metformin) that cannot be paused during the study.
6. History of another active malignancy within the past 5 years (except for specific cured cancers).
7. Toxicities from prior therapy have not recovered to acceptable levels.
8. Presence of symptomatic or uncontrolled brain metastases, carcinomatous meningitis, or spinal cord compression.
9. Symptomatic and uncontrolled third-space fluid accumulations (e.g., pleural effusion, ascites).
10. Severe cardiovascular/cerebrovascular disease or risk factors (e.g., heart failure, history of myocardial infarction, QT prolongation, uncontrolled hypertension, etc.).
11. History or presence of interstitial lung disease, or drug/radiation-related pneumonitis.
12. Active autoimmune or inflammatory diseases.
13. Active, uncontrolled infection (including HBV, HCV, HIV, syphilis, tuberculosis, etc.).
14. Gastrointestinal disorders or surgery affecting drug ingestion or absorption.
15. Active keratitis or ulcerative keratitis.
16. History of hypersensitivity to the study drug, its analogs, or chemotherapy drugs (pemetrexed/platinum agents).
17. Recent administration (within 30 days) of a live attenuated vaccine.
18. Psychiatric disorders or substance abuse potentially affecting compliance.
19. Any other condition deemed by the investigator as unsuitable for study participation.

Where this trial is running

Guangzhou

• Sun Yat-Sen University Cancer Center — Guangzhou, China (RECRUITING)

Study contacts

• Study coordinator: Haimeng Li

Conditions: Non-Small-Cell Lung Cancer, Non-Small-Cell Lung Cance, EGFR, PACC, L861Q, Lung Cancer, EGFR ex20ins