A Data-Driven Approach to Guide Representative Clinical Trial Enrollment and Retention Among Patients With Follicular Lymphoma and Marginal Zone Lymphoma.

Background:

Achieving representative clinical trial enrollment is critical for reducing bias and health disparities, and ensuring that efficacy and safety outcomes of novel treatments are generalizable to broad populations. Minority groups are often under-represented in clinical trials, and differences in clinical outcomes by race and ethnicity have been reported in B-cell non-Hodgkin lymphoma (B-NHL). To address this disparity, the US Food and Drug Administration (FDA) previously required submission of Diversity Action Plans (DAPs) to support Phase 3 and other pivotal clinical studies. Per this guidance, DAPs had to include study enrollment goals disaggregated by race, ethnicity, sex, and age, the rationale for these goals, and an explanation of how they will be met.

Odronextamab, a CD20×CD3 bispecific antibody, is being investigated in a large, global, multicenter, Phase 3 program (OLYMPIA) in patients with indolent and aggressive B-NHL. For the OLYMPIA-1 (NCT06091254), OLYMPIA-2 (NCT06097364), and OLYMPIA-5 (NCT06149286) studies, DAPs were developed prospectively at the start of participant recruitment to ensure representative enrollment.

Design and Methods:

OLYMPIA-1, -2, and -5 are ongoing, open-label, randomized studies comparing odronextamab monotherapy or combination therapy to standard of care in patients with previously untreated follicular lymphoma (FL), or relapsed/refractory FL or marginal zone lymphoma (MZL).

Under-represented populations in the US were projected by race, ethnicity, sex, and age distribution among patients with FL and MZL using Surveillance, Epidemiology, and End Results Program (SEER) data. For non-US countries, race and ethnicity projections were made using country-level data sources, such as census data, whereas sex and age distributions were assumed to match US SEER data.

Specialty site networks and real-world data were used to select sites with access to under-represented patients. Broadened eligibility criteria for the OLYMPIA-1, -2, and -5 studies allow enrollment of patients with controlled human immunodeficiency virus, hepatitis B or C, and renal impairment, which may occur more frequently in ethnic and racial minority groups. Participant education materials include racially representative imagery and are available in various formats and languages to support equitable access. To reduce the burden of study participation, travel support is provided for on-site visits, and outpatient treatment and telephone follow-ups are offered.

Enrollment per participant race and ethnicity distribution is being compared with planned enrollment at ~25%, 50%, and 75% of enrollment. If enrollment of any demographic group is lagging, additional actions such as focused site visits and outreach to specific patient groups, healthcare professionals, and community leaders will be implemented to boost study awareness.

Status:

Recruitment for OLYMPIA-1, -2, and -5 is ongoing, and we are optimistic that the measures in place will help to ensure that the study populations represent the real-world populations of people with FL and MZL.

Trademarked Items

Odronextamab (Ordspono)