Rationale and background: For the approval of new drug products or label expansions, conducting clinical trials that are fully representative of all potential patient subgroups is

challenging. In the case of label expansions, where trials have been conducted across one or more previously approved indications, pooling of existing safety data across all available clinical trials (regardless of indication) can yield greater sample sizes that may support safety characterization among subgroups of interest. Recently, the application to expand the brentuximab vedotin (BV) label to include large B-cell lymphoma provided an opportunity to apply this pan-indication safety pooling approach.

Research question and objectives: The objective of this study was to evaluate the distribution of safety events separately by race, ethnicity, and region among subjects in the

BV integrated clinical trial database, across any indication, either monotherapy or combination therapy. Methods: Safety data from 25 BV trials were pooled to tabulate a summary of treatment-emergent adverse events (TEAEs): treatment-emergent serious adverse events (TESAE), any TEAE, > grade 3 TEAE, TEAE leading to death, and discontinued treatment due to TEAE by race/ethnicity (Hispanic, non-Hispanic White, non-Hispanic Black), and region (US,ex-US).

Results: More subjects from the pooled dataset resided in the US (n=1886 subjects from US, n=683 ex-US), and the most common cancer under treatment was Hodgkin's Lymphoma (65.7% of monotherapy trials subjects and 40.2% of combination therapy trial subjects). There were 2217 total subjects in the pooled dataset with available data on race and ethnicity (n=1094 from BV monotherapy trials, n=1123 from BV combination therapy trials). Most patients (83%) were non-Hispanic White in both the monotherapy and combination therapy trials. The proportion of male subjects varied across trial type and racial/ethnic subgroup; 41.6%non-Hispanic Black subjects, BV monotherapy, to 57.6% non-Hispanic white, BV combination therapies. The average age of participants also varied across trial type and racial and ethnic subgroups, from a mean age of 42.7 years among Hispanic subjects in the BV monotherapy trials, to a mean age of 53.6 years among non-Hispanic White subjects in the BV combination therapy trials.

Reporting of any TEAE occurred across all racial and ethnic subgroups, ranging from 91.7% of Hispanic subjects in BV monotherapy trials, to 98.5% of non-Hispanic Black subjects in the BV combination therapy trials. Reporting of TESAEs was similar across racial and ethnic groups and by region: after pooling BV monotherapy and combination therapy subjects, TESAEs were reported among 31.7% of Hispanic subjects, 34.2% of non-Hispanic Black subjects, 32.9% of non-Hispanic White subjects, 32.8% of US subjects, and 36.5% ex-US subjects. The rates observed for the other TEAE categories examined (> grade 3 TEAE, TEAE leading to death, and discontinued treatment due to TEAE) were also similar across categories of race, ethnicity, and geographic region.

Discussion: The pooled data suggest the safety profile in racial and ethnic minority groups was broadly comparable to the data observed in non-Hispanic White subjects. The safety profile of BV (as monotherapy or as part of a combination therapy) within the racial and ethnic minority groups is largely consistent with the established and integrated safety profile of BV in the general adult population. This approach of pooling safety data across trials, across indications, may be helpful for other studies where subgroups of interest are of limited size within indication-specific clinical trials.

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2025
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