NCT07402343

Tarlatamab for SCLC Brain Metastases

A Single Arm Phase II Study Evaluating Intracranial Efficacy of Tarlatamab in Patients With Asymptomatic Active Brain Metastases From Small Cell Lung Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Sponsor: Maastricht University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A single arm phase II study evaluating intracranial efficacy of tarlatamab in patients with asymptomatic active brain metastases from small cell lung cancer (SCLC).

Detailed description

Patients with small cell lung cancer (SCLC) have a high risk of brain metastases (BM). Due to the decline in the use of prophylactic cranial irradiation (PCI), because of the risk of toxicity in absence of a survival benefit, as well as increased imaging follow-up, the incidence of BM in SCLC will rise compared to the PCI-era. Upon central nervous system (CNS) progression on first line therapy, cranial radiotherapy can be given but effect is modest. All standard of care second line drugs have limited (prolonged) efficacy in the CNS, or efficacy is unknown. Therefore, new systemic therapies that are active systemically as well as intracranially are needed. Tarlatamab is a bispecific T-cell engager targeting delta-like ligand 3 (DLL3) and CD3 and has shown promising activity in heavily pretreated patients with SCLC. With a median follow-up of 20.7 months, objective response rate (ORR) was 40% in a phase II trial, DCR was 70%, median PFS was 4.3 months, median OS 15.2 months and 26% had sustained disease control ≥52 weeks. The most common adverse event was cytokine release syndrome (CRS, 53% in the 10 mg group), with the majority being grade 1-2, and 1% grade 3. Similar long-term follow-up data was reported for the phase I trial. CNS disease progression occurred in only 9/112 enrolled patients (25% had baseline BM). Seventeen patients with previously treated BM with a size of ≥ 10mm were enrolled. Modified Response Assessment in Neuro-Oncology (RANO) criteria showed CNS tumor shrinkage ≥30% in 59% (10/17) of these patients, and intracranial disease control in 94%. Out of the 10 patients with CNS tumor shrinkage of ≥30%, five had cranial radiotherapy \>5 weeks before the start of tarlatamab, which indirectly indicates that tarlatamab could have intracranial activity. Additionally, the confirmatory randomized phase III trial DeLLphi-304 (NCT05740566) enrolling patients with relapsed SCLC and randomizing between tarlatamab and standard of care chemotherapy was positive for its primary outcome, OS. Median OS was 13.6 months for tarlatamab and 8.3 months for standard of care (hazard ratio 0.60, 95% confidence interval 0.47-0.77, p \<0.001). Additionally, tarlatamab resulted in a PFS benefit as well as less treatment related toxicity. Moreover, patients with (treated) BM derived at least the same magnitude of benefit (HR for OS with baseline BM 0.45, HR for OS if no baseline BM 0.81). At the end of the enrollment, the protocol was amended to allow patients with asymptomatic untreated BM. However, meaningful data regarding CNS efficacy of tarlatamab will not be obtained in this study. Therefore, it is of interest to evaluate tarlatamab in patients with SCLC with disease progression including BM on first line systemic therapy.

Conditions

• Small Cell Lung Cancer
• Brain Metastases, Adult

Interventions

Type	Name	Description
DRUG	Tarlatamab	Cycle 1: 1 mg on day 1, followed by 10 mg on days 8 and 15 Cycles thereafter: 10 mg every two weeks, in cycles of 28 days Treatment continues till unacceptable toxicity or disease progression

Timeline

• Start date: 2026-02-01
• Primary completion: 2029-02-01
• Completion: 2030-02-01
• First posted: 2026-02-11
• Last updated: 2026-03-04

Locations

4 sites across 1 country: Netherlands