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 recommended phase 2 dose of D3S-002 given orally in adult patients with advanced solid tumors that have mutations in the mitogen-activated protein kinase MAPK pathway. This first-in-human study includes different parts assessing D3S-002 alone or combined with D3S-001 in patients with specific tumor types, including non-small cell lung cancer without certain genetic mutations. The study has two main parts Part 1 is a dose escalation phase where D3S-002 is given orally alone. Part 2 includes a dose escalation phase and a dose expansion phase where participants receive both D3S-002 and D3S-001 orally. Treatments are given in 21-day cycles, and doses are adjusted to find the recommended phase 2 dose. Participants will be monitored from the first dose up to 24 months, with assessments including adverse events, dose-limiting toxicities, and pharmacokinetic measurements such as drug concentrations in the blood. Tumor response will also be evaluated using standardized criteria. Safety, tolerability, and effectiveness measurements will be collected throughout the study, and participants may be followed for up to two years after starting treatment.

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 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.

This research aims to evaluate the effectiveness and safety of plixorafenib in participants with cancers that have specific BRAF gene alterations. These include locally advanced or metastatic solid tumors, primary central nervous system tumors, and rare BRAF V600E-mutated solid tumors such as anaplastic thyroid, ovarian, and cholangiocarcinoma cancers. The study focuses on participants with BRAF V600E mutations or BRAF fusions and seeks to understand treatment effects across various cancer types. Participants receive plixorafenib orally in continuous 3-week cycles. Dosing may be increased as tolerated and continues until disease progression, unacceptable side effects, or withdrawal for other reasons. The study includes different subprotocols tailored to tumor type and BRAF alteration, such as unresectable solid tumors with BRAF fusions, recurrent primary CNS tumors with BRAF V600E mutations, rare non-CNS solid tumors with BRAF V600E mutations, and other advanced solid tumors with BRAF V600E mutations. Participants will undergo scans before starting treatment to assess tumor changes, and regular monitoring will continue during treatment. Researchers will evaluate tumor response, progression-free survival, overall survival, treatment safety, and drug levels in the blood over up to approximately four years. The study tracks side effects and collects detailed pharmacokinetic data to understand how the drug is processed. Participants remain in the study until disease progression or other withdrawal criteria are met, with ongoing safety and efficacy assessments.

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.

Researchers are investigating the molecular genetic similarity between primary tumors and brain metastases in patients with colorectal cancer. This observational study focuses on patients who have developed brain metastases, a rare and serious complication occurring in less than 3% of colorectal cancer cases. The study aims to better understand the genetic profiles of these tumors by analyzing specific gene mutations and their concordance between original and metastatic sites. The study involves molecular genetic testing of archival tumor samples collected from neurosurgical resections. Researchers will analyze mutations in KRAS, NRAS, BRAF, HER2 genes, and microsatellite instability MSI using specialized sequencing and immunohistochemical methods. This testing compares paired samples from both the primary colorectal tumor and its brain metastases to calculate how closely their genetic profiles match. Participants tumor samples will be examined for mutations and gene expressions using advanced laboratory techniques. The main outcome measured is the concordance rate of genetic mutations between the two tumor sites within one month. Secondary outcomes include monitoring intracranial progression-free survival and overall survival at intervals up to six months. The study involves no active treatment but detailed genetic and clinical follow-up over time to improve understanding of metastatic colorectal cancer biology.