KEY TAKEAWAYS
- The DeLLphi-300 phase 1 trial aimed to assess long-term outcomes and intracranial activity of tarlatamab in previously treated SCLC patients.
- The primary endpoint was safety.
- The extended DeLLphi-300 follow-up showed tarlatamab’s lasting responses and survival benefits in SCLC, warranting deeper intracranial efficacy investigation.
Targeting delta-like ligand 3 (DLL3), tarlatamab, a bispecific T cell engager (BiTE®) immunotherapy, exhibited lasting antitumor effects in small cell lung cancer (SCLC).
Horst-Dieter Hummel and the team aimed to present the DeLLphi-300 phase I study’s long-term results and intracranial response assessments.
Tarlatamab was assessed in previously treated SCLC patients, with eligibility for those with treated, stable brain metastases. Safety served as the primary endpoint, while secondary endpoints included objective response rate (ORR) based on mRECIST 1.1 by investigators, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
In retrospective exploratory analyses, the sum of diameters (SOD) of CNS tumors was evaluated per mRANO-BM by BICR in patients with at least one brain lesion at baseline. This report, with a data cutoff of 14.5 months beyond Paz-Ares et al.’s publication in J Clin Oncol 2023, included fully enrolled cohorts of patients treated with clinically relevant doses (≥ 10 mg) of tarlatamab.
About 152 patients received tarlatamab at doses of ≥ 10 mg, with a follow-up period ranging from 0.2 to 34.3 months (median 12.1 months). Across all cohorts, the ORR was 25.0%, with a mDOR of 11.2 months. Total 25 patients had treatment durations of ≥ 52 weeks (range 52–150), including 8 patients treated for ≥ 104 weeks. The mPFS was 3.5 months, and the mOS was 17.5 months, with PFS and OS estimates at 12 months of 16.7% and 57.9%, respectively.
Among the 16 patients with baseline CNS lesions ≥ 10 mm, a decrease of ≥ 30% in CNS tumor SOD was observed in 10 patients (62.5%). Additionally, of the 8 patients who completed brain radiotherapy (RT) at least 50 days before starting tarlatamab, 3 patients (37.5%) experienced a ≥ 30% decrease in CNS tumor SOD. No new safety signals were detected.
The extended observation of the DeLLphi-300 trial revealed tarlatamab’s enduring responses and remarkable survival benefits in recurrent SCLC. Although confined to assessing stabilized brain metastases, the notable reduction in CNS tumors post-tarlatamab treatment, even following radiotherapy, underscores the necessity for deeper investigation into tarlatamab’s efficacy against intracranial disease.
The trial was sponsored by Amgen.
Clinical Trial: https://clinicaltrials.gov/study/NCT03319940
Hummel H, Champiat S, Olmedo Garcia ME, et al. (2024) “Tarlatamab in previously treated small cell lung cancer (SCLC): DeLLphi-300 phase I study long-term outcomes and intracranial activity.” Presented at ELCC 2024, Annals of Oncology (2024) 9 (suppl_3): 1-11. 10.1016/esmoop/esmoop102577 (195MO).
