DETERMINE Treatment arm 5 (vemurafenib and Cobimetinib) aims to evaluate the efficacy of vemurafenib and cobimetinib in adult patients with rare* cancers with BRAF V600 mutations or in common cancers where BRAFV600 mutations and considered to be infrequent.~*Rare is defined generally as incidence less than 6 cases in 100,000 patients 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 where promising activity is identified 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 cancers.~OUTLINE:~Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the participant based on molecularly-defined cohorts.~Screening: Consenting participants undergo biopsy and collection of blood samples for research purposes.~Treatment: Participants will receive vemurafenib and cobimetinib until disease progression, unacceptable toxicity or withdrawal of consent. Participants will also undergo collection of blood samples at various intervals while receiving treatment and at 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.
This clinical trial is looking at a combination of drugs called vemurafenib and cobimetinib. Vemurafenib is approved as standard of care for adult patients with unresectable or metastatic melanoma. Cobimetinib is approved as standard of care in combination with vemurafenib for the treatment of adult patients with unresectable or metastatic melanoma.~Cobimetinib and vemurafenib work in patients with these types of cancers which have certain changes in the cancer cells called BRAF V600 mutation-positive.~Investigators now wish to find out if it will be useful in treating patients with other cancer types which are also BRAF V600 mutation-positive. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.~This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.