BRAF Gene Mutation

Researchers are investigating metastatic colorectal cancer (mCRC) patients who have a specific genetic change called the BRAFV600E mutation. This rare subtype of mCRC often shows poor response to current treatments and has a generally poor outlook. The study aims to collect detailed clinical data and biological samples to better understand this condition, including how patients respond to treatments and what factors predict their survival. It focuses on real-world treatment outcomes and biological markers that might influence therapy choices and resistance. Participants will provide blood samples at multiple times during their treatment, including before and during the first three treatment cycles, at 3 and 6 months after starting each treatment line, and when disease progression occurs following certain therapies. The study gathers up to 390 mL of blood per participant over time to analyze circulating tumor DNA and immune environment factors. This observational approach will help researchers identify biomarkers related to treatment response and disease progression. During the study, participants' clinical progress and survival will be tracked for up to five years. Researchers will review overall survival from diagnosis to death and assess how prognostic markers relate to progression-free survival and response to treatments. The study involves collecting tumor tissue samples and blood tests, along with routine follow-up visits. All data collected will contribute to understanding BRAFV600E mCRC and improving future treatment strategies.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and appropriate dosing of D3S-002 in adults with advanced solid tumors that have mutations in the MAPK pathway. This first-in-human study aims to find the recommended phase 2 dose of D3S-002 given daily by mouth in 21-day cycles. The study includes adults with metastatic or locally advanced solid tumors or non-small cell lung cancer with specific genetic mutations and prior treatment history. The study has two main parts: Part 1 involves dose escalation of D3S-002 given orally as a single drug. Part 2a also involves dose escalation but tests D3S-002 together with another oral drug, D3S-001. Part 2b is a dose expansion phase where the combination of D3S-002 and D3S-001 is further evaluated. Both drugs are taken by mouth, and participants receive treatment cycles lasting 21 days each. Participants will be monitored for adverse events starting from the first dose until 30 days after their last dose, with ongoing assessments up to 24 months. Researchers will measure drug levels in the blood, responses to treatment using specific tumor evaluation criteria, and progression-free survival. Safety, tolerability, and pharmacokinetics are closely tracked throughout the study. Participants must adhere to study visits and provide tumor and blood samples for genetic analysis when required.

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 the safety of avutometinib as a treatment for children and young adults aged 3 to 30 years with advanced or recurrent solid tumor cancers, including pediatric tumors with specific genetic alterations affecting the MAP kinase pathway and certain neurofibromatosis conditions. This phase 1 study aims to find the highest dose of avutometinib that is safe and causes few or mild side effects. Participants receive oral avutometinib twice a week, once daily, in cycles of three weeks on treatment followed by one week off, with each cycle lasting 28 days. The study uses a dose-escalation design, starting at Dose Level 1 and adjusting the dose based on the number of dose-limiting toxicities (DLTs) observed, to identify the maximum tolerated dose (MTD). During the study, participants will be closely monitored for safety over up to 12 months. Researchers will assess side effects and tolerability, and participants will undergo regular evaluations including clinical assessments and laboratory tests. The study carefully tracks adverse events and adjusts dosing to ensure participant safety throughout the trial.

Researchers are conducting a real-world, multicenter observational study to better understand metastatic colorectal cancer (mCRC) patients in China who have the BRAFV600E mutation. Previous studies showed that patients with this mutation tend to have shorter survival times compared to those without it, but data specific to Chinese patients on mutation rates, diagnosis, prognosis, and survival are limited. This study aims to fill those gaps by collecting detailed information on these aspects. The study will observe patients with the BRAFV600E mutation who started treatment for mCRC between October 1, 2020, and October 1, 2025. Treatments involved are those registered for mCRC at the participating centers, but this is a non-interventional study, meaning researchers will not assign treatments but will record existing treatment patterns and regimens. There are no experimental drugs or placebos involved. Participants will be monitored for various outcomes including progression-free survival over 6 months, overall survival over 24 months, and overall response rate at 6 months. Data will be collected retrospectively from multiple centers to capture treatment effectiveness and safety in real-world settings. The study is sponsored by Fudan University and is expected to continue through October 2026.

Researchers are evaluating the safety and effectiveness of plixorafenib in people with advanced or metastatic solid tumors, including primary central nervous system tumors, that have specific BRAF gene alterations. The study focuses on participants with BRAF fusions or rare BRAF V600 mutations in tumors like melanoma, thyroid cancer, or recurrent CNS tumors. This is a Phase 2 trial aiming to understand how well plixorafenib works in these cancer types. Participants receive plixorafenib as oral tablets continuously in 3-week cycles. The dose may be increased as tolerated and treatment continues until the disease progresses, unacceptable side effects occur, or other reasons lead to stopping. The study includes different groups based on tumor types and BRAF mutation status, including unresectable solid or CNS tumors with BRAF fusions, recurrent CNS tumors with BRAF V600E mutations, and advanced rare non-CNS solid tumors with BRAF V600E mutations. During the trial, participants will have scans and tests before starting treatment to assess tumor changes. Researchers will monitor tumor response, duration of response, progression-free survival, overall survival, and treatment side effects for up to four years. Blood samples will be taken to study how the drug is processed in the body. Participants will be closely followed throughout the study to evaluate the drug's effects and safety.

Researchers are evaluating the safety, pharmacokinetics, and preliminary effectiveness of NST-628, an oral drug targeting the MAPK pathway, in adults with advanced solid tumors that have specific genetic mutations and have exhausted standard treatments. This Phase 1, open-label, multi-center study includes patients with tumors dependent on the MAPK pathway, such as melanoma and glioma, aiming to find a suitable dose and observe tumor responses. The study has two parts: Part A involves dose escalation where increasing doses of NST-628 are given once daily in 28-day cycles to determine the maximum tolerated dose and the recommended dose for expansion. Part B involves dose expansion with several cohorts of patients harboring specific MAPK pathway mutations receiving the recommended dose to further assess safety and tumor response. Dose adjustments may be made based on observed effects. Participants will undergo regular assessments including safety evaluations, tumor response measurements using standardized criteria, and pharmacokinetic analyses throughout the study, which lasts about one year on average for primary outcomes and up to two years for survival monitoring. Tumor tissue samples are required, and patients will be followed until the last visit of the final participant. Safety, tumor response, progression-free survival, overall survival, and drug behavior in the body are key outcomes measured.

Researchers are studying the rate and timing of melanoma disease relapse after neoadjuvant therapy, focusing on whether participants achieve a complete pathologic response or not, and how postoperative adjuvant treatments affect outcomes. This early phase 1 trial targets patients with advanced melanoma that has a BRAF V600 mutation and evaluates different adjuvant therapies based on individual response to initial treatment. Participants will first receive 24 weeks of neoadjuvant oral encorafenib and binimetinib before planned surgery. After surgery, participants with a complete pathologic response may receive either 24 more weeks of encorafenib and binimetinib or another adjuvant treatment for 24 weeks. Those without a complete response will continue either encorafenib and binimetinib or receive nivolumab for 24 weeks. Imaging scans will be done every 12 weeks for at least one year post-surgery, then every 24 weeks for up to two additional years. During the study, participants will undergo regular imaging to monitor for disease relapse and response to treatment. Researchers will track relapse rates, survival, and response to therapy over several years. Safety and laboratory tests will also be conducted to ensure participant health. The total follow-up period includes evaluations after surgery for at least 24 weeks, with survival tracking up to five years.

Researchers are studying Canadian cancer patients who have rare genetic changes in their tumors, such as alterations in genes like ALK, EGFR, ROS1, BRAF, and KRAS G12C. These rare molecular alterations can affect how the cancer responds to certain targeted drugs called tyrosine kinase inhibitors (TKIs). The study aims to better understand the natural history of these cancers and compare treatment outcomes, including side effects and patient-reported experiences, across different therapies. The study observes cancer patients who have received or are currently receiving TKIs or other targeted therapies. It includes three groups: living patients with confirmed rare molecular alterations, deceased patients with such alterations, and a comparator group of cancer patients without these rare changes. Patient-reported outcomes are collected through surveys at baseline and every three months, especially when treatments change. Participants provide molecular testing reports and complete quality of life questionnaires regularly for up to 10 years. Researchers track progression-free survival or overall survival, the development of brain metastases, and economic impacts related to treatment. The study collects data from medical records and patient surveys to understand treatment patterns, effectiveness, and quality of life in the real-world Canadian context.

Researchers are evaluating the effect of preoperative targeted therapy using dabrafenib and trametinib in patients with conventional ameloblastoma of the jaw who have the BRAF V600E mutation. The main goal is to see if this treatment can shrink tumors enough to allow for mandibular preservation surgery instead of segmental resection and to determine if cases initially not suitable for complete removal become operable. This is a Phase 2 single-arm clinical study focused on improving surgical outcomes for this condition. Participants receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily, taken orally with specific timing instructions related to meals and dose intervals. Treatment is given in 30-day cycles, with evaluations after the first two cycles to monitor tumor shrinkage, drug safety, and side effects. If toxicity is intolerable or the tumor progresses, participants may switch to traditional surgery. Follow-up continues every two cycles until surgery is feasible or tumor shrinkage plateaus. During the study, participants undergo consultations, physical exams, imaging studies, and laboratory tests to assess safety and treatment response. Researchers measure the proportion of patients able to have mandibular preservation surgery and those whose tumors become resectable after therapy. Secondary outcomes include radiological and pathological responses, local recurrence-free survival over three months, and monitoring adverse effects for up to 12 months. The total study duration and safety monitoring extend through these periods to ensure comprehensive evaluation.