DETERMINE arm 04: trastuzumab with pertuzumab in HER2-amplified or mutated rare cancers

DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial, NCT05786716) is a Cancer Research UK umbrella-basket platform for rare adult, paediatric and teenage and young adult cancers with actionable genomic alterations, including common cancers with rare alterations. Treatment arm 04 gives trastuzumab with pertuzumab to patients whose tumours carry HER2 amplification or activating mutations; the registry conditions include gallbladder neoplasms alongside haematological, colorectal, bladder, salivary, lung, pancreatic, ovarian, prostate and skin cancers. Primary outcomes are objective response and durable clinical benefit; 30 patients are planned in this arm with primary completion in October 2029. The arm follows the MyPathway finding of a 23 percent response rate with the same pair in HER2-positive biliary tract cancer and is the route to dual HER2 antibody therapy for UK patients with HER2-amplified gallbladder cancer outside a company trial.