Tests metformin added to targeted drugs in lung cancer with EGFR mutations
Tests metformin with targeted lung cancer drugs in adults with EGFR-mutated non-small cell lung cancer.
Plain-language title generated from the registry record
Registry title: Metformin Plus Tyrosine Kinase Inhibitors for Treatment of Patients With Non-small Cell Lung Cancer With EGFR Mutations
Key facts
- Where
- Mexico City, MexicoSee the site
- Phase
- Phase 3
Where in Mexico
- Instituto Nacional de CancerologiaMexico City, MexicoTaking people
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Instituto Nacional de Cancerologia de Mexico
- Trial code
- NCT05445791
- Record updated
- 9 April 2026
- Original description
Lung cancer is the most common neoplastic disease globally, with over 2 million new cases annually, accounting for 11.6% of all cancer diagnoses. It remains the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) makes up 80-85% of lung cancer cases, with most patients diagnosed at an advanced stage. Five-year survival rates are low, ranging from 8-18% worldwide.Read full original descriptionShow less
Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone for Patients With Advanced Non-small Cell Lung Cancer and EGFR Mutations: Phase 3 Randomized Clinical Trial
Lung cancer is the most common neoplastic disease globally, with over 2 million new cases annually, accounting for 11.6% of all cancer diagnoses. It remains the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) makes up 80-85% of lung cancer cases, with most patients diagnosed at an advanced stage. Five-year survival rates are low, ranging from 8-18% worldwide.
Advances in molecular biology have led to the identification of therapeutic targets in NSCLC. One of the most studied is the epidermal growth factor receptor (EGFR), a key regulator of tumor cell functions and a focus of targeted therapy development. EGFR mutations occur in about 15% of NSCLC cases globally but reach up to 34% in Mexico. Patients with these mutations are treated with tyrosine kinase inhibitors (TKIs), which improve response rates and progression-free survival (PFS) over chemotherapy. However, resistance to TKIs typically develops, prompting the need for strategies to overcome this challenge and extend PFS.
Up to 30% of NSCLC patients have somatic mutations in the liver kinase B1 (LKB1) gene, a tumor suppressor that inhibits mTOR. In one study, 24 patients with LKB1 expression treated with metformin plus TKIs showed significantly improved overall survival. LKB1 activates AMP-activated protein kinase (AMPK), which regulates cell cycle and survival in NSCLC. Loss of LKB1 reduces AMPK activation and increases tumor necrosis following bevacizumab treatment. A study of 99 NSCLC samples linked high AMPK expression to poorer survival, though its role in metformin response is unclear.
Metformin, a biguanide used for type 2 diabetes, has shown anticancer properties. Studies suggest metformin reduces cancer incidence and mortality. In vitro, it induces G0/G1 cell cycle arrest and counters TKI resistance due to epithelial-mesenchymal transition (EMT). Retrospective studies support its benefit in NSCLC, and prospective trials of metformin plus TKIs have yielded mixed results.
This phase 3 randomized study aims to evaluate PFS in NSCLC patients with EGFR mutations treated with TKIs plus placebo versus TKIs plus metformin.
Inclusion: Patients with a histologically confirmed diagnosis of non-small cell lung cancer (stage IIIB-IV) according to the American Joint Committee on Cancer (AJCC) eight edition; Measurable disease by RECIST 1.1; 18 years of age or older; Functional status 0-2 as assessed by Eastern Cooperative Oncology Group (ECOG) scale; Life expectancy of minimum12 weeks; Patients with non-small cell lung cancer and a documented EGFR sensitizing mutation; Patients without previous EGFR-TKI treatment. Previous use of chemotherapy is allowed with a washout period of at least 6 months; Patients with asymptomatic brain metastases, or if symptoms are present treatment with radiotherapy (whole brain radiotherapy, stereotactic radiosurgery) or surgery must be administered; Neutrophil count ≥1.5 x 103/mm3, and platelet count >100 x (103/mm3); Serum bilirubin ≤1.5 the superior upper limit; Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2 superior upper limit (or ≤ 5 times the superior upper limit in patients with liver metastases); Serum creatinine ≤ 1.5 superior upper limit, or creatinine clearance ≥ 60ml/min; Full ability to complete all study procedures and follow up; Women with child-bearing potential must have a negative pregnancy test within 72 hours of treatment start; Patients with reproductive potential must use effective contraception; Signed informed consent for participation in the study; Availability of tumor tissue (pre-treatment biopsy) to determine LKB1 and AMPK status.
Exclusion: Patients diagnosed with any other neoplastic disease in the previous 5 years (except in situ cervical carcinoma or basocellular skin cancer, treated accordingly); Patients being currently treated with metformin; Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart disease, hepatic diseases, renal diseases); Patients unable to receive oral medication, who require IV nourishment, or who underwent surgical procedures with affect nutrient absorption, or with an active peptic ulcer; Patients previously treated with an EGFR-TKI; Patients diagnosed with type 2 diabetes or a glycated hemoglobin ≥ 6.5%; Pregnant or lactating women.