Tarlatamab in small cell lung cancer (SCLC): Safety and efficacy analyzed by baseline brain metastasis.

Stephane Champiat Gustave Roussy, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France info_outline Stephane Champiat, Michael J. Boyer, Ramaswamy Govindan, Luis G. Paz-Ares, Taofeek K. Owonikoko, Hossein Borghaei, Hiroki Izumi, Neeltje Steeghs, Fiona Helen Blackhall, Angelika Terbuch, Melissa Lynne Johnson, Tatsuya Yoshida, Kai He, Yuyang Zhang, Simon Jones, Xi Chen, Pablo Martinez, Horst-Dieter Hummel

Authors Stephane Champiat Gustave Roussy, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France info_outline Stephane Champiat, Michael J. Boyer, Ramaswamy Govindan, Luis G. Paz-Ares, Taofeek K. Owonikoko, Hossein Borghaei, Hiroki Izumi, Neeltje Steeghs, Fiona Helen Blackhall, Angelika Terbuch, Melissa Lynne Johnson, Tatsuya Yoshida, Kai He, Yuyang Zhang, Simon Jones, Xi Chen, Pablo Martinez, Horst-Dieter Hummel Organizations Gustave Roussy, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France, Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, Australia, Divisions of Hematology and Oncology, Washington University Medical School, St. Louis, MO, Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Ciberonc and Universidad Complutense, Madrid, Spain, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center, Pittsburgh, PA, Fox Chase Cancer Center, Philadelphia, PA, Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands, Department of Medical Oncology, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan, James Thoracic Oncology Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, Amgen Inc., Thousand Oaks, CA, Translational Oncology/Early Clinical Trial Unit (ECTU), Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Amgen Background: Tarlatamab, a BiTE molecule targeting DLL3 and CD3, is being studied in patients (pts) with extensive stage small cell lung cancer (ES-SCLC). 1 Up to 25% of pts diagnosed with SCLC have brain metastases (BM) and 50% or more will develop BM during the course of the disease. Pts with ES-SCLC and BM have poor prognosis and quality of life. We analyzed the characteristics and outcomes of pts included in the tarlatamab phase 1 study (NCT03319940) who had baseline BM vs those who did not. Methods: Pts included in the phase 1 trial had SCLC that progressed after ≥1 platinum-based regimen and received tarlatamab (0.003–100 mg IV). Pts with treated BM were eligible if local therapy was delivered ≥ 2 weeks prior to first tarlatamab dose. Results: As of 03 January 2023, 192 pts had received tarlatamab as monotherapy. Median age was 62 (range, 32–80) y; 188 pts (98%) had ECOG PS 0–1 and median prior therapy lines was 2 (range, 1–6), with 107 pts (56%) receiving prior anti-PD1/PD-L1. 48 pts (25%) had BM at screening and 142 (74%) did not (No BM); data was missing for 2 pts (1%). Pts with BM were more likely to have received > 3 prior lines of therapy (BM, 29%; No BM, 9%) and have a record of prior brain radiation (BM, 85%; No BM, 40%); otherwise, characteristics of pts with BM were generally similar to those without. Tarlatamab delivered comparable activity in pts with BM vs. those without in terms of objective response rate (ORR; 20%, 25%) and disease control rate (DCR; 59%, 50%) (Table). Median duration of response (DoR) was 14.9 months (BM) vs. 13.0 months (no BM). Median overall survival (OS) was 13.2 months in the BM group vs 15.5 months in the no BM group. Safety outcomes were similar in terms of treatment-related AEs (TRAEs; BM, 90%; No BM, 94%) and grade (gr) ≥ 3 (BM, 38%; No BM, 39%). Groups were also comparable with respect to immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events (any-grade, 6% vs 9%; gr ≥ 3, 4% vs 4%) and neutropenia (any-grade, 10% vs 15%; gr ≥ 3, 8% vs 8%). AEs numerically different in the BM vs No BM group included gr ≥ 4 TRAEs (17%, 7%) and any-grade CRS (67%, 54%). The only grade 5 TRAE (pneumonitis) occurred in the BM group. Conclusions: Tarlatamab continues to show promising efficacy and is generally safe in pts with ES SCLC irrespective of the presence of BM. Rates of ICANS and associated neurologic AEs were comparable between those with and without BM at baseline. Reference: 1. Paz-Ares L, et al. J Clin Oncol. DOI:10.1200/JCO.22.02823. Clinical trial information: NCT03319940. Efficacy in pts with and w/o BM, Interim efficacy analysis set. BM (n = 46) No BM (n = 136) ORR, n (%) 9 (19.6%) 34 (25.0%) DCR, n (%) 27 (58.7%) 68 (50.0%) DoR, median (95% CI)* 14.9 (3.8, NR) 13.0 (7.4, NR) PFS, median (95% CI) 3.7 (1.9, 4.8) 3.7 (1.9, 5.3) OS, median (95% CI) 13.2 (6.6, NR) 15.5 (10.6, NR) *BM, n=9; No BM, n=34 CI, confidence interval; DCR, disease control rate; NR, not reached; PFS, progression-free survival.

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