DeLLphi-301 Analysis: Tarlatamab Is Active in SCLC, Regardless of Baseline Brain Metastases

The bispecific T-cell engager tarlatamab showed promising efficacy in patients with small cell lung cancer (SCLC) both with and without baseline brain metastasis, according to results of a subgroup analysis of the DeLLphi-301 trial presented at the 2024 American Society of Clinical Oncology Annual Meeting.

“The efficacy and the safety of tarlatamab is exactly the same in patients with and without stable, treated brain metastases at baseline,” said study presenter Anne-Marie C. Dingemans, MD, PhD, of Erasmus MC Cancer Institute, the Netherlands.

The phase 2 study enrolled 186 patients with SCLC. Patients were randomly assigned to receive tarlatamab 10 mg or tarlatamab 100 mg during the dose evaluation stage, with tarlatamab 10 mg selected for dose expansion.

Initial results of DeLLphi-301 showed an overall response rate (ORR) of 40% with a median progression-free survival of 4.9 months and a median overall survival (OS) of 14.3 months. These data were the basis for the May 2024 FDA approval of tarlatamab.

Dr. Dingemans presented results from a subgroup analysis of 100 patients treated with tarlatamab 10 mg.  Of these 100 patients, 23 had baseline brain metastases. Only patients with confirmed brain metastases at baseline had mandated surveillance CNS imaging.

Tarlatamab demonstrated durable responses with promising survival, regardless of the presence of treated, stable brain metastases at baseline.

With a median follow-up of 10.6 months, the ORR was 52% in patients with brain metastases, compared with 38% in patients without brain metastases. The median duration of response was not reached in either group.

The median PFS was 6.7 months for patients with brain metastases compared with 4.0 months for those without. The median OS was an “encouraging” 14.3 months in patients with baseline brain metastases, Dr. Dingemans said.

Treatment-related adverse events were comparable between the study arms. Any grade of immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurological events occurred in 3% of patients with brain metastases and 5% of patients without brain metastases. No grade 3 or worse ICANS occurred.

A post-hoc analysis of intracranial activity for the combined 10 mg and 100 mg cohorts of patients with baseline CNS lesions of ≥10 mm showed CNS tumor shrinkage of at least 30% in 59% of patients, with intracranial disease control in 94%.

According to Dr. Dingemans, these results support further study of tarlatamab in patients with previously treated SCLC, regardless of brain metastases at baseline.

Reference

Dingemans A-M C, Ahn M-J, Blackhall FH, et al. DeLLphi-301: Tarlatamab phase 2 trial in small cell lung cancer (SCLC)—Efficacy and safety analyzed by presence of brain metastasis. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024, Chicago, Illinois.