Inclusion of people living with HIV in Food and Drug Administration (FDA) oncology pivotal registration trials from 2020 to 2024.

1517 Background: People living with HIV (PLWH) have an increased risk of developing cancers compared to the population without HIV, with cancer being the leading cause of death for this population in high-income countries. Previous research by the ASCO-led HIV working group found only 11% of clinical trials supporting FDA cancer therapy approvals from 2010-2014 allowed for inclusion of PLWH, leading to clinical uncertainty in the efficacy-safety profile of new cancer treatments in this group. To address this gap, ASCO (2017) and FDA (2020) issued guidelines encouraging inclusion of PLWH in cancer clinical trials. To explore their impact, we examined inclusion of PLWH in pivotal cancer trials post-guidelines release. Methods: We reviewed all new FDA-approved indications of the past five years (Jan/2020-Nov/2024). For each new approval, two authors independently assessed the inclusion/exclusion criteria outlined in the primary protocol of each pivotal trial. We analyzed data on the FDA label, cancer type, therapeutic modality, inclusion/exclusion criteria, sponsor, and the protocol (version 1) publication date. Results: We identified 244 new therapy indications, based on supporting data from 259 pivotal clinical trials. 27% of trials permitted inclusion of PLWH. Pivotal trials for hematological cancers, compared to solid cancers, were significantly more likely to exclude PLWH [unadjusted Odds Ratio (OR) 3.15, 95% confidence interval (CI): 1.51-6.56; p=0.0012]. Pivotal trials of immunomodulatory agents were significantly more likely (OR 3.87, 95% CI: 1.91–7.83; p<0.0001) to exclude PLWH compared to other cancer therapies. The inclusion rate was 10.3% for AIDS-defining cancers and 29.8% for non-AIDS-defining cancers. Trials funded only by industry were significantly more likely (OR 2.80, 95% CI: 1.36-5.77; p=0.0078) to exclude PLWH, compared to non-industry funded trials. Inclusion rate of PLWH was higher in protocols published after 2020 (39.1%) compared to those before (26.3%). Conclusions: Our analysis indicates an improvement in the inclusion of PLWH in oncology pivotal trials following ASCO and FDA guidance. However, nearly three out of four pivotal cancer trials continue to exclude PLWH. This highlights an unmet need, resulting in uncertainty for healthcare professionals regarding the safety and clinical utility of new cancer treatments in PLWH. Additional strategies must be considered to address this disparity. Rates of PLWH inclusion in oncology pivotal trials. Include PLWH (%) Total (n=259) 27.4 Solid Cancers (185) 33 Haematological malignancies (74) 13.5 Immunomodulatory agents (89) 12.4 Other agents*(170) 35.3 Industry-funded (223) 24.2 Non-industry funded (36) 47.2 AIDS-Defining Cancers (30) 10 Non-AIDS Defining Cancers (45) 29.8 * Chemotherapy, targeted therapy, drug-antibody conjugates, hormone therapy, radionuclide therapy.