Precision medicine aims to deliver the right drugs to the right patients at the right time. However, patients with rare cancers face significant challenges in accessing clinical trials, often due to limited trial availability near their homes. Decentralized clinical trials (DCTs) are emerging as a solution to this problem, bringing clinical trials closer to patients and reducing the burden of travel and associated costs.
The Unmet Need in Rare Cancer Trials
Rare cancers, defined as those with an incidence of fewer than six per 100,000 people, collectively account for approximately 22% of the cancer burden. Despite this significant impact, they receive disproportionately less funding compared to common cancers. Moreover, rare cancers are more prevalent among younger and nonwhite individuals, and their prognosis tends to be worse, potentially due to limited expertise, approved therapies, and clinical trials.
Tissue-Agnostic Biomarker-Driven Trials
In addition to rare cancers defined by incidence and histology, there exists another category of rare cancers characterized by rare tissue-agnostic genomic events. These tumors, regardless of their origin, share a common molecular abnormality. Targeted therapies directed at these abnormalities have demonstrated high response rates, leading to several tumor-agnostic biomarker-based FDA approvals in oncology, with response rates ranging from approximately 30% to 75%.
NCI-MATCH: A National Platform Trial
The National Cancer Institute–Molecular Analysis for Therapy Choice (NCI-MATCH) trial was the first national-scale platform clinical trial in the USA. It featured centralized diagnostic testing and geographically distributed clinical investigation of multiple treatment options in parallel. The trial enrolled 1,201 patients across 1,117 sites and evaluated 38 cohorts. NCI-MATCH demonstrated the feasibility of nationwide accrual of patients on a platform trial with multiple rare genomic basket subgroups across numerous histologies, with successful biopsy and enrollment at local facilities. Some matches, such as targeting PIK3CA with copanlisib and AKT1 E17K-mutated tumors with capiasertib, met the study response endpoints.
SWOG's DART Trial: An Immunotherapy Platform
The SWOG Cancer Research Network’s DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial is an immunotherapy platform for rare cancers. The study aimed to address the gap in immune checkpoint inhibitor trials for patients with rare cancers. The DART trial employed a single-arm two-stage phase II design for each cohort, with RECIST response as the primary endpoint. The study was open at over 1000 sites across the NCI’s SWOG National Cooperative Trial Network, enhancing accessibility for patients across the USA. To date, four cohorts of rare/ultra-rare cancers (metaplastic breast cancer, angiosarcoma, and two cohorts of neuroendocrine tumors) have been published, revealing a subset of highly immunotherapy-responsive patients. Approximately 10 additional cohorts have been presented at major national meetings, with some published cohorts influencing NCCN guidelines.
The Rise of Home-Run Trials
A "home-run" therapeutic clinical trial enables patients to receive novel treatments at home, either through decentralized, site-less patient care or through a large network of sites across the country. This approach addresses the challenges faced by patients with rare and ultra-rare cancers, improving access to potentially life-saving therapies and reducing the burden of participation.
