Matching-Adjusted Indirect Treatment Comparison of Tarlatamab Versus Comparator Therapies in England in Patients with Extensive-Stage Small Cell Lung Cancer Who Have Received Two or More Prior Lines of Therapy.

Introduction: The non-comparative phase 2 DeLLphi-301 trial found that tarlatamab, a bispecific T cell engager immunotherapy, can provide sustained objective response rates and improved survival outcomes for patients with previously treated extensive-stage small cell lung cancer (ES-SCLC). In the absence of direct head-to-head evidence, an indirect treatment comparison was conducted to estimate the efficacy of tarlatamab relative to comparator therapies in England.

Methods: The outcomes of patients in the DeLLphi-301 trial were compared against those of a comparator therapies cohort identified through linkage of population-level real-world databases in England. The study population consisted of patients with relapsed ES-SCLC who received two or more prior lines of therapy and who met key eligibility criteria from the DeLLphi-301 trial. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). An unanchored matching-adjusted indirect comparison (MAIC) was used to estimate the efficacy of tarlatamab relative to available comparator therapies, adjusting for key baseline characteristics to match the patient cohort from DeLLphi-301 with the comparator therapies cohort. A weighted Cox proportional hazards model with robust variance estimation was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for both OS and PFS.

Results: The analyses included 97 patients enrolled in the DeLLphi-301 trial and 540 patients receiving available treatment options in England. After matching, tarlatamab was associated with improved OS (HR 0.24; 95% CI 0.14, 0.43) and PFS (HR 0.18; 95% CI 0.11, 0.31) relative to the comparator therapies. Findings were similar in sensitivity analyses performed by changing the variables for adjustment.

Conclusion: Tarlatamab provides a clinically meaningful survival benefit compared to currently available treatments in England. These findings support the use of tarlatamab as an effective treatment option for patients with previously treated ES-SCLC.