Tarlatamab with first-line chemo-immunotherapy for extensive-stage small cell lung cancer: DeLLphi-303 study
1Early Clinical Trial Unit, Medical Clinic and Poliklinik I, Carl Gustav Carus University Hospital, Dresden, Germany; 2NYU Langone Perlmutter Cancer Center, New York, NY, USA; 3Rabin Medical Center, Petah Tikva, Israel; 4Department of Pulmonary Diseases, AZ Delta Hospital, Roeselare, Belgium; 5Department of Medical Oncology, Providence Swedish Cancer Institute, Seattle, WA, USA; 6Department of Medical Oncology, Centre L.on B.rard, Lyon, France; 7Department of Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany; 8Hospital Universitario 12 de Octubre, CNIO-H12O Lung Cancer Unit, Complutense University and CIBERONC, Madrid, Spain; 9Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 10Chris O’Brien Lifehouse, Sydney, Australia; 11Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 12Amgen Inc., Thousand Oaks, CA, USA; 13Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain
Background:
Tarlatamab with anti-PD-L1 achieved notable survival outcomes with manageable safety as maintenance therapy following 1L platinum-etoposide chemotherapy and anti-PD-L1 (1L chemo-IO) for extensive stage small cell lung cancer (ES-SCLC). In this phase 1b study (parts 2, 4, 7), the safety and efficacy of adding tarlatamab to 1L chemo-IO was assessed.
Objectives:
- Describe the clinical rationale for adding tarlatamab to first-line chemoimmunotherapy in patients with extensive ES-SCLC.
- Evaluate the safety profile and preliminary efficacy outcomes of tarlatamab combined with chemoimmunotherapy as reported in the DeLLphi-303 study.
Methods:
Patients (pts) had received 1 cycle of 1L chemo- IO prior to enrollment. On study, pts received 3 cycles of tarlatamab + 1L chemo-IO followed by tarlatamab + anti-PD-L1 Q3W until progression. Tarlatamab was administered 20 mg Q3W with a 1 mg step dose. Primary endpoints included dose-limiting toxicities (DLTs), treatment-emergent (TE), and treatment-related (TR) adverse events (AEs). Key secondary endpoints were objective response (OR), duration of response (DOR), progression- free survival (PFS), and overall survival (OS).
Results:
Of 96 pts enrolled, 3 (3%) had DLTs. TEAEs and TRAEs were reported in all pts. The most common TRAEs were cytokine release syndrome (CRS, 56%), anemia (54%), and dysgeusia (46%). Grade (Gr) ≥ 3 TRAEs occurred in 72 pts (75%), most commonly neutropenia/neutrophil count decreased (44%), anemia (23%), and lymphopenia/lymphocyte count decreased (11%), primarily within the first two cycles. CRS (54% Gr 1-2; 2% Gr 3-4) and ICANS and associated neurological events (5% Gr 1-2; 1% Gr 3) TRAEs were mostly low grade. Other immune-related AEs were rare (2%). From a baseline scan after 1 cycle of 1L chemo-IO, OR rate following tarlatamab addition to 1L chemo-IO was 71%, with median DOR of 11.0 months (mo) (95% CI 6.7-not estimable). Median PFS was 9.0 mo. With a median follow-up time of 11.3 mo, the Kaplan-Meier estimate of OS at 12 mo was 81%. Results from further follow-up will be presented.
Conclusions:
The combination of tarlatamab with chemo-IO for 1L treatment of ES-SCLC demonstrated manageable safety with encouraging initial survival outcomes, supporting further investigation of this combination in the phase 3 DeLLphi-312 study.
Funding: Amgen Inc.
Prior Presentations:
Presented at the European Society for Medical Oncology (ESMO) Congress 2025, October 17-21, Berlin, Germany.
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