Tarlatamab Sustained Clinical Benefit Among Previously Treated Patients With Small Cell Lung Cancer

Updated Results From the DeLLphi-300 Trial

According to extended follow-up results from the DeLLphi-300 trial, tarlatamab sustained clinical benefit among previously treated patients with small cell lung cancer (SCLC). 

“Tarlatamab is a bispecific T-cell engager (BiTE) immunotherapy that redirects cytotoxic T cells to cancer cells expressing delta-like ligand 3 (DLL3), resulting in cancer cell lysis,” stated Afshin Dowlati, MD, University Hospitals Seidman Cancer Center, Cleveland, Ohio, and coauthors. “In phase I/II studies, tarlatamab demonstrated durable anticancer activity with a manageable safety profile in patients with previously treated SCLC.”

In this open-label, dose-escalation study, researchers enrolled 152 patients (including 72 patients from the initial report and 80 patients not included in the initial report) with previously treated, asymptomatic SCLC with (n = 38) or without brain metastases to receive  ≥10 mg of tarlatamab administered either once every 2 weeks, once every 3 weeks, or once on days 1 and 8 of a 21-day cycle. The primary end point was safety. Key secondary end points included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

At a median follow-up of 12.1 months, the ORR was 25% with 4 complete responses and 34 partial responses. The median DOR was 11.2 months (DOR ≥ 12 months = 13; DOR ≥ 24 months = 4) and 31.6% of patients had ongoing response. The median PFS was 3.5 months, and the median OS was 17.5 months. Sustained disease control was observed in 15.1% of patients.  Among patients who received 10 mg once every 2 weeks (the phase 2 dose) the ORR was 35.3%, the median DOR was 14.9 months, the median OS was 20.3 months, and 29.4% of patients had sustained disease control. 

No new safety signals were observed, and safety data was consistent with prior findings. Treatment-related adverse events occurring in ≥ 20% of patients included pyrexia, nausea, fatigue, decreased appetite, and dysgeusia. Among patients who continued tarlatamab beyond 1 year, 34.8% of patients experienced grade 1 or 2 late-onset treatment-related cytopenia or asthenia and 1 patient experienced grade 3 late-onset treatment-related neutropenia, which led to dose reduction and was resolved. 

“In this extended follow-up of DeLLphi-300, tarlatamab showed a sustained clinical benefit,” concluded Dr Dowlati et al. “Tarlatamab's survival benefit compared with the standard of care is being assessed in second-line SCLC in the DeLLphi-304 phase III trial.” 

Source: 

Dowlati A, Hummel HD, Champiat S, et al. Sustained clinical benefit and intracranial activity of tarlatamab in previously treated small cell lung cancer: DeLLphi-300 trial update. J Clin Oncol. Published online August 29, 2024. doi: 10.1200/JCO.24.00553