KEY TAKEAWAYS
- DeLLphi-301 is a Phase 2 open-label study (NCT05060016) to evaluate the efficacy of tarlatamab in pretreated SCLC patients.
- This study assessed anticancer activity, safety, immunogenicity, pharmacokinetics, and overall survival up on intake of tarlatamab
- The researchers used randomized assignment to one of two tarlatamab dose groups to characterize dose-response.
- 27 % of patients experienced treatment-related adverse events (AEs) of grade 3 or higher, and 5% discontinued therapy due to AEs.
Small cell lung cancer (SCLC) is distinguished by its rapid development and early metastasis formation. Despite a high initial response rate, illness recurrence is prevalent following platinum-based first-line chemotherapy. The delta-like ligand 3 (DLL3) is a notch ligand elevated and abnormally expressed on the cell surface in most SCLC, making it a promising therapeutic target. T cell activation and expansion and T cell-dependent death of tumor cells are induced by the HLE BiTE immuno-oncology medication tarlatamab by binding DLL3 on target cancer cells and CD3 on T cells, producing a cytolytic synapse. Tarlatamab’s preliminary evidence for efficacy in pretreated patients with relapsed/refractory SCLC (NCT03319940) includes 20% verified partial responses and duration of response of 8.7 mo (Owonikoko TK, et al. Abstract 8510). (Presented at ASCO Annual Meeting, June 4–8, 2021; Virtual) 27 % of patients experienced treatment-related adverse events (AEs) of grade 3 or higher, and five percent discontinued therapy due to AEs. Tarlatamab’s favorable performance and safety profile in SCLC warrants additional research.
Tarlatamab has been the subject of phase 2, open-label research (NCT05060016) examining its efficacy in patients with relapsed/refractory SCLC who have already been exposed to two or more lines of treatment. In Part 1, subjects will be randomly assigned to one of two tarlatamab dose groups to characterize the dose response. Based on the intermediate analysis from Part 1, enrolment in Part 2 will proceed exclusively for the particular target dose.
Patients must have had two or more lines of prior treatment, including at least one platinum-based regimen (including a PD-L1 inhibitor, if the standard of care, with certain exceptions per protocol), have had brain metastases treated, have an ECOG performance status of 1, and have an investigator-assessed survival time of fewer than 12 weeks to be eligible for this study.
ORR, according to RECIST 1.1, as evaluated by a blinded independent central review, is the primary endpoint for the primary analysis. Secondary goals include assessing anticancer activity in terms of safety and tolerability, immunogenicity, pharmacokinetics, and overall survival, in addition to the duration of response, progression-free survival, rate and duration of disease control, and overall survival. The trial is international, with sites in North America, Asia, and Europe recruiting participants.
Source: https://meetings.asco.org/abstracts-presentations/213233
Clinical trial:https://clinicaltrials.gov/ct2/show/NCT05060016
Ramalingam, S. S., Ahn, M.-J., Akamatsu, H., Blackhall, F. H., Borghaei, H., Hummel, H.-D., Johnson, M. L., Reck, M., Zhang, Y., Jandial, D., Cheng, S., & Paz-Ares, L. G. (2022). Phase 2 study of tarlatamab, a DLL3-targeting, half life–extended, bispecific T-cell engager (HLE BiTE)immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC). Journal of Clinical Oncology, 40(16_suppl), TPS8603–TPS8603. https://doi.org/10.1200/jco.2022.40.16_suppl.tps8603
