EGFR Gene Mutation

Researchers are evaluating the effectiveness of combining JMT101, a recombinant humanized anti-EGFR monoclonal antibody, with osimertinib, an EGFR tyrosine kinase inhibitor, compared to osimertinib alone. This Phase 3, randomized, positive-controlled, open-label study focuses on patients with newly diagnosed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has EGFR-sensitive mutations. The aim is to assess whether the combination improves treatment outcomes for this specific lung cancer type. Participants receive either JMT101 intravenously every two weeks along with daily oral osimertinib, or osimertinib alone taken orally daily. Each treatment cycle lasts four weeks. This study is designed to compare these two treatment approaches as first-line therapy for the specified lung cancer patients. Treatment and monitoring continue for up to approximately 44 months after the first participant is enrolled. During the study, participants undergo regular assessments including imaging scans evaluated by an independent review committee using RECIST 1.1 criteria to measure progression-free survival and other response rates. Researchers also monitor overall survival, adverse events, and immune responses to JMT101. Laboratory tests assess blood counts, organ function, and antibody levels. The study includes ongoing safety monitoring and long-term follow-up visits to evaluate treatment effects and tolerability.

Pancreatic neuroendocrine neoplasms (pNENs) are tumors with increasing incidence and limited treatment options, especially after disease progression or drug resistance from current therapies like somatostatin analogues, chemotherapy, and targeted drugs. Existing treatments such as sunitinib and everolimus have shown limited clinical efficacy with low objective response rates. Researchers are investigating new combinations, including sorafenib and gefitinib, based on evidence linking the EGFR pathway to tumor progression and poor survival in pNEN patients. This study evaluates a single treatment group receiving oral sorafenib (250mg) and gefitinib (250mg) daily, each dose taken once a day. Treatment cycles last 4 weeks, aiming to explore the effectiveness and safety of this combination for patients with pNENs who have progressed after prior treatments. Sorafenib is a tyrosine kinase inhibitor targeting VEGFR, FGFR1, and CSF1R, which may help inhibit tumor angiogenesis and regulate immune responses, while gefitinib targets EGFR. Participants will be assessed regularly with imaging every 8 weeks to measure tumor response and progression-free survival, with survival assessments every 12 weeks up to two years. Safety and tolerability of the drug combination will also be evaluated over two years. The study involves a screening process, treatment period, and follow-up evaluations to monitor outcomes and side effects, supporting comprehensive observation of the treatment's impact on disease progression.

Researchers are investigating the characteristics and clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients in Asia who have a specific genetic change called EGFR exon 20 insertion mutation. This study aims to improve understanding of how different forms and locations of this mutation affect patient responses to new targeted therapies. It addresses a current gap in detailed knowledge about this condition in the Asian population. This is a multi-center observational study enrolling about 600 patients retrospectively from various countries across Asia, including Hong Kong, Korea, Singapore, Taiwan, and Thailand. Patients included have advanced NSCLC with confirmed EGFR exon 20 insertion mutations identified through approved local tests. The study does not involve experimental treatments but collects data on patients' clinical management and outcomes. Participants' medical records will be reviewed to gather information on survival, therapy durations, and disease progression over up to 10 years. The primary measures include overall survival, duration of therapy, and real-world progression-free survival. This long-term data collection will help researchers better understand the disease course and treatment effectiveness in this patient group.

Researchers are evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and early anti-tumor activity of increasing doses of EPI-326 in patients with locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This Phase 1 study is the first to test EPI-326 in humans and aims to understand how the drug behaves and affects these cancers. Participants will receive EPI-326 as a single agent through intravenous infusion in a dose escalation design to find the recommended dose and schedule. Treatment will continue until the disease progresses, unacceptable side effects occur, the participant withdraws consent, or the study ends. The study is open-label and conducted at multiple centers. During the study, participants will be monitored for safety and tolerability of EPI-326 for up to three years. Blood samples will be taken to measure drug levels and how the body processes it. Researchers will also assess tumor response, including the objective response rate and duration of response. Participants' organ function and overall health status will be evaluated regularly to ensure safety throughout the study period.

Researchers are evaluating JIN-A02, a fourth-generation EGFR-TKI oral medication, in people with advanced non-small cell lung cancer (NSCLC) that has specific EGFR mutations and has progressed after standard treatments. This Phase I/II open-label study focuses on assessing the safety, tolerability, pharmacokinetics, and anti-tumor activity of JIN-A02 in those who have previously received approved EGFR-TKI therapy and/or platinum-based chemotherapy. The study includes multiple parts to explore dosing and treatment effects based on mutation types. The study has three parts: Part A is a dose escalation phase using a Bayesian Optimal Interval design to find the maximum tolerated dose (MTD) in patients with EGFR mutations C797S or T790M. JIN-A02 is given once daily in 28-day cycles, with dose adjustments based on safety evaluations. Part B further explores two selected dose levels to determine the recommended Phase 2 dose (RP2D). Part C expands treatment to five cohorts defined by specific EGFR mutation profiles, monitoring anti-tumor activity using the established RP2D. Participants undergo regular assessments including safety reviews by a committee, tumor mutation testing from tissue or plasma samples, and monitoring for adverse events and dose-limiting toxicities. The study measures outcomes such as maximum tolerated dose, adverse event rates, and dose-limiting toxicities over specified timeframes. The study duration and follow-up depend on the dose-escalation, exploration, and expansion phases with ongoing data collection for safety and benefit-risk analysis.

Researchers are evaluating the safety, tolerability, and early anti-tumor activity of a combination of two drugs, ABSK043 and Firmonertinib, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation in the EGFR gene. This Phase 2, open-label study focuses on patients with EGFR-mutated NSCLC and aims to find the best dose and schedule while closely monitoring patient safety. The study has two parts: Part A is a dose escalation phase that includes patients who have previously received treatment and experienced disease progression; Part B is a dose expansion phase involving patients who have not yet received systemic therapy for advanced disease. ABSK043 is given orally at either 400 mg or 800 mg twice daily, while Firmonertinib is given orally at a fixed dose of 80 mg once daily. Treatment cycles last 21 days, and patients continue therapy until disease progression, unacceptable side effects, withdrawal, or study end. Participants will undergo regular safety monitoring including assessments for dose-limiting toxicities, adverse events, serious adverse events, and specific side effects from the time they consent until up to 30 months after their last dose. Researchers will also measure progression-free survival at 12 months. Pharmacokinetic tests and tumor response evaluations are conducted during treatment. The total study duration per participant varies based on treatment response and safety outcomes.

Researchers are evaluating the safety, tolerability, pharmacokinetics (PK), and effectiveness of GH21 capsules combined with Osimertinib mesylate tablets in patients with advanced non-small cell lung cancer (NSCLC) that has EGFR mutations. This study includes phase Ib, phase IIa, and phase IIb stages to determine the recommended dose and assess how patients respond to this combination treatment. In phase Ib, a classic "3+3" design is used to select dose levels with four preset dose groups including once daily (QD) and twice weekly (BIW) dosing schedules. Phase IIa consists of two cohorts receiving different doses of GH21 combined with Osimertinib 80 mg QD, while phase IIb involves one cohort where dose and treatment decisions are based on safety, efficacy, and PK data from earlier phases. Participants will be monitored for adverse events, dose-limiting toxicities, and progression-free survival over two years. Assessments include tumor measurements using RECIST 1.1 criteria, genetic testing, survival rates, and plasma drug concentration levels. The study also tracks overall safety, treatment response, and pharmacokinetics to understand how the drugs behave in the body during and after treatment.

This research aims to evaluate the effectiveness and safety of combining sacituzumab tirumotecan with furmonertinib in patients who have locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with specific EGFR mutations. These patients have experienced progression after treatment with EGFR-TKI therapies and platinum-based chemotherapy. The study builds on previous findings that showed promising benefits with similar drug combinations in this patient population. Participants receive sacituzumab tirumotecan at a dose of 5 mg/kg through intravenous infusion on days 1 and 15 of each treatment cycle, along with daily oral doses of furmonertinib mesylate at 80 mg. The study will monitor patients over a period of up to 24 months to assess progression-free survival, overall survival, response rates, duration of response, quality of life, and safety. Throughout the study, participants will undergo regular assessments including tumor tissue or biopsy for biomarker analysis, laboratory tests to monitor organ and cardiac function, and questionnaires to evaluate quality of life. Safety and treatment responses will be closely monitored up to 24 months. The study requires patients to have adequate organ function and an ECOG performance status of 0 or 1, with expected survival beyond six months, ensuring they can comply with study procedures and visits.

Colorectal cancer with the BRAF V600E mutation is a serious condition linked to poor outcomes, especially in patients with metastatic disease that is microsatellite stable (MSS). This trial explores a new combination of drugs targeting BRAF mutations, EGFR, and immune checkpoints to improve treatment options for these patients. It is an open-label Phase II study focusing on safety and effectiveness. The study evaluates a combination treatment including sintilimab (an anti-PD-1 drug), ipilimumab N01 (an anti-CTLA-4 drug), cetuximab (an anti-EGFR drug), and dabrafenib (a BRAF inhibitor). Participants receive these drugs following specific schedules: ipilimumab N01 is given intravenously every 6 or 12 weeks with maintenance dosing, sintilimab every 3 weeks, cetuximab every 2 weeks, and dabrafenib orally twice daily. The trial includes both first-line and second-line treatment groups. Participants will be closely monitored throughout the study with assessments including tumor measurements and laboratory tests to evaluate progression-free survival over up to 2 years. Other outcomes include disease control rate, response rate, overall survival, and tracking of treatment-related side effects for up to 3 years. The study starts in March 2026 and continues through June 2028, with visits and evaluations scheduled regularly to track participants’ response and safety.

Researchers are evaluating zorifertinib as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) that has mutations in the EGFR gene and has spread to the central nervous system (CNS). This prospective study involves multiple centers and compares the survival benefits and safety of zorifertinib to other similar drugs called EGFR tyrosine kinase inhibitors (EGFR-TKIs). The study aims to better understand how well zorifertinib works and its clinical value in this patient group. Participants are divided into three groups: those receiving first-line zorifertinib who meet criteria of the EVEREST study, those receiving zorifertinib but not meeting EVEREST criteria, and those receiving other anti-tumor drugs chosen by their doctors excluding zorifertinib. The EVEREST study is an open-label trial comparing zorifertinib to gefitinib or erlotinib. Treatments are given as prescribed by clinicians, with monitoring of safety and dosage adjustments as needed. During the study, participants will be followed for up to 36 months, with assessments every 8 weeks to measure overall survival, progression-free survival, intracranial progression, response rates, and adverse events. Researchers will track dose changes and monitor safety outcomes over time. The study collects clinical data to evaluate the effectiveness and tolerability of the treatments in patients with EGFR-mutant advanced NSCLC and CNS metastases.