(261) CARMA-BROS: An efficient Basket/Umbrella Real-world Observational Study (BUROS) Design for Rare Cancer Subtypes

Publication Number: 921

Background: BUROS is an emerging innovative design for the generation of real-world evidence in malignancies with rare molecular aberrations.

Objectives: To highlight the efficiency of BUROS design for the study of cancers with rare molecular alterations and different histologic subtypes.

Methods: CARMA-BROS is an academia-led BUROS that can add different observational arms. We reviewed study elements, protocol, coordination, funding, and research output of CARMA-BROS (NCT04151342) and compared it to traditional observational studies regarding cost and logistical benefits, flexibility, funding models, and research outputs.

Results: In 2019, CARMA-BROS initially had funded arms for lung cancer patients with ALK fusions, rare EGFR exon 20 insertion mutations, BRAF mutations, and ROS1 fusions. In 2020, an arm opened for EGFR common mutations in lung cancer and was funded in 2021 by another pharmaceutical company. In 2022, a third arm was funded for KRAS G12C mutations in lung cancer. It took 20 months to set up CARMA-BROS from inception to first site opening, and 15 Canadian sites have been added during COVID-19 pandemic over 19 months, with only one more original site left to open, covering 6 of the 7 largest provinces by population; 7 new sites (which would cover the 8 most populous provinces) have expressed interest or started site initiation. Importantly, the second and third industry partners required only 6 and 5 months from initial discussion to opening. The third industry partner required a short turnaround for health technology assessment, and had a completed arm from first discussion to results delivery in 10 months, involving 10 sites (5 provinces). Academic partners identified lower coordinator burden, faster start-up of new arms, and ease of contract and ethics amendments as benefits of BUROS. Industry partners cited single contract with coordinating center, quick turnaround, and significant cost savings, when compared to traditional sponsored multi-site observational studies. Data from initial arms have been submitted to Health Canada, CADTH, EMA-UK, EMA-France, and to regulatory agencies in Bulgaria and China, with 3 publications since 2020. Currently, there are new academic/industry arms opening for small-cell lung cancer, NTRK pan-cancers, rare gastrointestinal and head and neck cancer subtypes (appendiceal, peritoneal mesothelioma, biliary, gastroesophageal, nasopharyngeal cancers), demonstrating the flexibility of this study design.

Conclusions: BUROS offers several logistic and clinical benefits compared to conventional designs and can serve as a new model for observational cancer studies in Canada, with the capacity to expand to multiple disease sites.