DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.

DETERMINE Treatment Arm 07 (dabrafenib and trametinib) aims to evaluate the efficacy of dabrafenib and trametinib adult, paediatric and TYA patients with rare\* cancers with BRAF V600 mutations or with common cancers where BRAF V600 mutations are considered to be infrequent. \*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers. OUTLINE: Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the patient based on molecularly-defined cohorts (See information on Master Screening Protocol below). Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes. Treatment: Patients will receive dabrafenib and trametinib until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at End of Treatment (EoT). After completion of study treatment, patients are followed up every 3 months for 2 years. THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.