441O - A platform trial with a registry study for rare cancers: MASTER KEY project

Abstract

BackgroundRare cancers have had a challenge in establishing standard therapies for patients compared to major cancers, due to the lack of basis for clinical studies and investigations. We started a biomarker driven basket/umbrella trial using a “master protocol”, called the MASTER KEY Project, which aims to find more efficient ways to evaluate treatments for rare cancers. MethodsThe project opened in April 2017 and consists of a prospective registry study part and a multiple clinical trials part. Patients with advanced rare cancers (annual incidence <6 / 100,000 population)/cancers of unknown primary/rare tissue subtypes of common cancers, undergoing a molecular diagnostic testing are enrolled. The primary objective of the registry study is to collect consecutive data on biomarker, patient background, and prognosis to build a database highly reliable for use as historical control data in future clinical trials. Sub-studies are placed under a “master protocol”, and each sub-study will enroll patients with the appropriate biomarker, regardless of tumor type. ResultsAs of Feb. 2019, 515 patients were enrolled in the project, and 493 were available for their backgrounds. Most frequent cancer types were: soft tissue sarcomas (33.7%), neuroendocrine tumors (7.3%), tumors of CNS (5.9%), salivary gland tumors (4.5%), etc. 346 patients had next generation sequencing testing results. The most common alterations were TP53 (32.4%), KRAS (10.4%), PIK3CA (9.5%), MDM2 (5.2%), CDK42 (4.9%), CDKN2A (4.9%), and RB1 (4.9%). 278 patients already had 6 months follow-up, and 116 patients received 181 systemic chemotherapy regimens after enrollment. Of those regimens, 25 were biomarker-based therapies, and median progression free survival was 8.1 months compared to 4.8 months with other cytotoxic chemotherapy regimens (Hazard ratio 0.61; 95% confidential interval 0.32-1.07). ConclusionsMASTER KEY Project is one of the largest platform trials focused only on rare cancers. The project provided the chance for rare cancer patients to receive biomarker-based treatment, and it showed better prognosis. This is a continuous project aimed to accelerate treatment development for rare cancers, with clinical trials directed towards new drug approvals. Clinical trial identificationUMIN000027552. Legal entity responsible for the studyThe authors. FundingAstellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Kyorin Pharmaceutical, Novartis Parma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Taiho Pharmaceutical and Takeda Pharmaceutical. DisclosureAll authors have declared no conflicts of interest.