Comparing the Standard of Care With Tarlatamab in Relapsed Small Cell Lung Cancer: DeLLphi-304

SCLC is a rapidly progressing cancer that initially responds to first-line therapy but almost always relapses, and prognosis for these patients is poor due to limited second-line treatment options. Tarlatamab is a bispecific T-cell engager molecule that engages both CD3 on T cells and delta-like ligand 3 on SCLC cells, leading to T-cell-mediated lysis of SCLC cells.

Previous results from the phase 1 DeLLphi-300 study of tarlatamab in patients with heavily pretreated relapsed or refractory SCLC showed a manageable safety profile, along with antitumor activity and an encouraging response durability. This trial was followed by the phase 2, open-label DeLLphi-301 study that evaluated patients with advanced SCLC treated with a platinum-based regimen and one other line of therapy. Results from DeLLphi-301 and updated details of the phase 3 trial in progress were presented at the 2023 North America Conference on Lung Cancer.

Results from the phase 2 study showed that tarlatamab at a dose of 10 mg every 2 weeks demonstrated anticancer activity, with an overall response rate of 40% and a manageable safety profile in patients with previously treated SCLC. DeLLphi-304 is a global, open-label, randomized phase 3 trial that will evaluate the efficacy and safety of tarlatamab against SOC in approximately 700 patients with relapsed SCLC following platinum-based first-line chemotherapy, with a goal of providing clarity on long-term response durability and survival benefits.

Patients are randomized 1:1 to receive tarlatamab or SOC (lurbinectedin or topotecan or amrubicin per local SOC), stratified by prior anti-PD-L1 treatment, chemotherapy-free interval, presence of brain metastases, and SOC (topotecan/amrubicin vs lurbinectedin). The primary objective is to compare the efficacy of tarlatamab with SOC in prolonging OS. Key secondary end points include comparison of PFS and patient-reported outcomes. Eligibility criteria include adults with histologically or cytologically confirmed relapsed SCLC who progressed following one platinum-based regimen, along with measurable lesions per Response Evaluation Criteria in Solid Tumors 1.1 and adequate organ function. Enrollment is currently ongoing (NCT05060016).

Source: Paz-Ares L, Felip E, Ahn M-J, et al. Trial in progress: randomized phase 3 study of tarlatamab, a DLL3-targeting bispecific T-cell engager (BiTE), compared to standard of care in relapsed small cell lung cancer (DeLLphi-304). Abstract of a poster presented at the 2023 North America Conference on Lung Cancer; December 1-3, 2023; Chicago, Illinois.