Dr Johnson on the Initial Efficacy of Ifinatamab Deruxtecan in Refractory SCLC

Melissa L. Johnson, MD, director, Lung Cancer Research, Sarah Cannon Research Institute; chair, Oncology Department, member, Medical Executive Committee, TriStar Centennial Medical Center, discusses findings from a subgroup analysis of outcomes with ifinatamab deruxtecan (I-DXd; DS-7300) in patients with refractory small cell lung cancer (SCLC), which she presented at the 2023 IASLC World Conference on Lung Cancer.

A phase 1/2 trial (NCT04145622) was conducted to assess the efficacy of I-DXd in heavily pretreated patients with various advanced solid tumors who were unselected for B7-H3 expression. After a median follow-up of 11.7 months, a subgroup analysis of response rates, survival outcomes, and responses based on B7-H3 expression was conducted in the SCLC cohort from part 1 of the study. Patients treated with a dose level of 6.4 mg/kg or less were deemed evaluable for efficacy in the subgroup analysis.

Results showed that I-DXd produced robust, durable responses in this patient subset (n = 22), Johnson states. A reduction in target lesions was seen in nearly all patients with post-baseline scans. At a median follow-up of 11.7 months, the objective response rate with I-DXd was 52.4%, and the median duration of response was 5.9 months. The median progression-free survival (PFS) was 5.6 months, and the median overall survival (OS) was 12.2 months. No new safety signals were observed with I-DXd and the regimen was deemed tolerable, she notes.

Amongst evaluable patients for in the B7-H3 analysis, B7-H3 expression was moderate to high, Johnson continues. No trends of association between best overall response, OS, or PFS and B7-H3 positivity or intensity were observed. Future confirmatory studies of I-DXd will be needed with a larger sample size to further assess the absence of this correlative relationship, Johnson states.

Overall, these findings support the ongoing phase 2 study (NCT05280470) of patients with second- or third-line extensive stage SCLC from this cohort, Johnson concludes.