In an extended follow-up analysis of the DeLLphi-300 phase I study, tarlatamab demonstrated long duration of response (DoR), overall survival (OS), and a subset of patients with sustained disease control with time on treatment ≥52 weeks. With tarlatamab 10 mg once every two weeks, the dose selected for future trials, the objective response rate (ORR) was 35.3%, the median DoR 14.9 months, the median OS 20.3 months, and 29.4% of patients had sustained disease control. Such efficacy is promising relative to current second-line treatment options and even front-line chemo-immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC).
With tarlatamab treatment, central nervous system (CNS) tumour shrinkage of ≥30% occurred in 62.5% of patients who had baseline CNS lesions ≥10 mm, including in a subset long after previous brain radiotherapy. No new safety findings were identified. The findings are published by Dr. Afshin Dowlati of the University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland, OH, US and colleagues on 29 August 2024 in the JCO. The findings were previously presented in part at the European Lung Cancer Congress (ELCC) on 22 March 2024 in Prague, Czech Republic.
The authors wrote in the background that while most patients with ES-SCLC respond to front-line therapy, disease progression often occurs within 6 months. Current second-line treatments impart short DoR with median of 3.3-5.3 months and median OS of 5.8-9.3 months. Tarlatamab is a bispecific T-cell engager immunotherapy that redirects cytotoxic T-cells to cancer cells expressing delta-like ligand 3 (DLL3), resulting in cancer cell lysis. In phase I DeLLphi-300 and phase II DeLLphi-301 studies, tarlatamab demonstrated durable anticancer activity with a manageable safety profile in patients with previously treated SCLC.
In the latest article published in the JCO, DeLLphi-300 study team reports findings from extended follow-up with a median follow-up of 12.1 months (range, 0.2-34.3) in fully enrolled cohorts treated with tarlatamab ≥10 mg dose administered once every two weeks, once every three weeks, or once on day 1 and once on day 8 of a 21-day cycle among total of 152 patients. Overall, the ORR was 25.0%, the median DoR was 11.2 months (95% confidence interval [CI 6.6 to 22.3], and the median OS was 17.5 months (95% CI 11.4 to not estimable [NE]).
Among 17 patients receiving 10 mg tarlatamab once every two weeks, the ORR was 35.3%, the median DoR 14.9 months (95% CI 3.0 to NE), the median OS 20.3 months (95% CI 5.1 to NE), and 29.4% had sustained disease control with time on treatment ≥52 weeks.
In modified Response Assessment in Neuro-Oncology Brain Metastases analyses, CNS tumour shrinkage of ≥30% was observed in 62.5% of patients (10 of 16) who had a baseline CNS lesion of ≥10 mm, including in a subset of patients with tumour shrinkage long after previous brain radiotherapy.
The authors commented while these findings must be considered in the context of limitations including requirement for previous therapy and lack of mandatory CNS imaging to identify asymptomatic brain metastases, these results suggest potential intracranial activity of tarlatamab. Further study on intracranial efficacy of tarlatamab is needed, including mechanisms underlying potential CNS activity, which, if validated, may be related to increased permeability of the blood brain barrier in patients with brain metastases and CNS infiltration by activated T-cells as seen in patients treated with blinatumomab.
Survival benefit of tarlatamab compared with the standard-of-care is assessed in second-line SCLC in the DeLLphi-304 phase III study.
The study was supported by Amgen Inc.
Reference
Dowlati A, Hummel H-D, Champiat S, et al. Reference Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update. JCO; Published online 29 August 2024. DOI: https://doi.org/10.1200/JCO.24.00553