Phase 2 DeLLphi-301 Study Results of Tarlatamab in Previously Treated SCLC

New immunotherapeutic approaches are being investigated in small cell lung cancer (SCLC). Tarlatamab is a bispecific T-cell engager that binds to both delta-like ligand 3 (DLL3) on SCLC cells and CD3 on T cells to elicit T-cell–mediated tumor lysis. Based on encouraging safety and antitumor activity from early studies, the DeLLphi-301 study was initiated to further evaluate tarlatamab in previously treated SCLC; phase 2 data from this study presented at the 2023 ESMO annual meeting are summarized here.

The DeLLphi-301 study enrolled patients with SCLC previously treated with 2 or more lines of therapy. In part 1 of the study (dose evaluation), eligible patients received either tarlatamab 1 mg (on day 1) followed by 10 mg on days 8, 15, and every 2 weeks thereafter, or tarlatamab 1 mg (day 1) followed by 100 mg on days 8, 15, and then every 2 weeks. In part 2 (dose expansion), patients received tarlatamab 10 mg every 2 weeks. Part 3 included a reduced inpatient monitoring period and patients received tarlatamab 10 mg every 2 weeks. The primary end point was objective response rate (ORR) by blinded independent central review (RECIST 1.1). Other end points were duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.

A total of 222 patients were enrolled in the study and received tarlatamab monotherapy: 100 patients in parts 1 and 2 (tarlatamab 10 mg), 88 in part 1 (tarlatamab 100 mg), and 34 in part 3 (tarlatamab 10 mg). Thirty-three percent of patients in parts 1 and 2 (10 mg), 43% in part 1 (100 mg), and 35% in part 3 (10 mg) had ≥3 prior lines of therapy.

At a median follow-up of 10.6 months, 100 patients included in the 10-mg dose cohort and 88 in the 100-mg dose cohort were evaluable for efficacy. At the 10-mg dose, an ORR of 40.0% was achieved including 1 complete response (CR) and 39 partial responses (PRs); median PFS was 4.9 months, median OS was 14.3 months, and median DoR was not reached. At the 100-mg dose, ORR was 31.8% including 7 CRs and 21 PRs; median PFS was 3.9 months, and median OS and median DoR were not estimable.

Cytokine release syndrome was the most common treatment-emergent adverse event (AE), occurring in 49% of patients in the 10-mg dose cohort and 61% of patients in the 100-mg dose cohort; these occurred predominantly in cycle 1 and were mostly grade 1 or 2. Immune effector cell–associated neurotoxicity syndrome was infrequent and occurred predominantly with tarlatamab 100 mg. There were no grade 4 or 5 events. Discontinuations due to treatment-related AEs occurred in <4% of patients in both dose cohorts.

Based on these results, the authors concluded that tarlatamab monotherapy demonstrated antitumor activity, durable responses, and emergence of no new safety signals in previously treated SCLC, warranting further evaluation in larger controlled studies in this setting.

Source:

Luis P-A. Tarlatamab for patients (pts) with previously treated small cell lung cancer (SCLC): primary analysis of the phase 2 DeLLphi-301 study. Abstract presented at: ESMO Annual Meeting, October 20-24, 2023; Madrid, Spain. Abstract LBA92.