Abstract B133: Characterization of FDA Regulatory Designations and Trial Models for Rare Cancer Approvals (2012–2022)

Abstract Purpose: Although there is no universally accepted definition for a rare cancer, the Orphan Drug Act defines a rare disease or condition as one which affects less than 200,000 people in the United States (U.S). The National Institute of Health defines rare cancers as those that affect fewer than 40,000 people in the U.S., and many cancer types are even rarer. Between 1987 and 2011, the U.S. FDA approved 45 drugs for 68 rare cancer indications, supported by 99 clinical trials. The regulatory framework and therapeutic strategies for rare cancers have transformed over the past decade. This study explores U.S. Food and Drug Administration (FDA) orphan drug designations for hematological malignancies from 2012 to 2025, with a focus on pivotal trial designs, therapeutic advancements, and patient populations. Methods: A retrospective analysis was conducted using FDA databases, including the Orphan Drug Product Designation list and approved drug labels. All oncology drugs granted orphan designation for hematological malignancies within the study period were systematically evaluated. We excluded drugs approved for supportive care (e.g., antiemetics, hematopoiesis-stimulating agents). The primary objective is to characterize and analyze clinical trial designs, cancer and sub cancer classifications, approval types, and patient populations for drugs approved by the FDA for rare cancer indications between June 2011 and May 2025. Results: Our preliminary analysis revealed 54 orphan designation instances corresponding to 18 unique generic drugs, with designation grants peaking in 2016. The designations were predominantly for Non-Hodgkin Lymphoma (n=24) and Multiple Myeloma (n=10). A paradigm shift in therapeutic modality was evident, the majority of approvals were cell therapies (43%) and small molecules (37%). This trend was driven by agents targeting key tumor biomarkers such as CD19, BTK, and BCMA. Moreover, a majority of these approvals (52%) were based on data from single-arm clinical trials, and the intended patient population was almost adult (94%). Conclusions: These findings highlight a fundamental shift in the development of drugs for rare hematological cancers, moving precisely toward precision medicine. The significant reliance on single-arm trials reflects a transformative regulatory approach designed to accelerate the availability of novel therapies addressing critical unmet medical needs for patients with few treatment options. Citation Format: Tariq E. Alzahrani, Albandari A. Alnasser, Alhanouf Y. Alnafisah, Aljawharah A. Albati, Manal F. Almutairi, Meshal A. Al-Kalabi, Shatha A. Almuhaidib, Tariq H. Alqurayshah. Characterization of FDA Regulatory Designations and Trial Models for Rare Cancer Approvals (2012–2022) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B133.