Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer

Author(s): Myung-Ju Ahn, M.D., Ph.D., Byoung Chul Cho, M.D., Ph.D., Enriqueta Felip, M.D., Ph.D., Ippokratis Korantzis, M.D., Kadoaki Ohashi, M.D., Ph.D., Margarita Majem, M.D., Ph.D., Oscar Juan-Vidal, M.D., Ph.D., Sabin Handzhiev, M.D., Hiroki Izumi, M.D., Ph.D., Jong-Seok Lee, M.D., Ph.D., Rafal Dziadziuszko, M.D., Ph.D., Jürgen Wolf, M.D., et al., for the DeLLphi-301 Investigators*
Source: N Engl J Med 2023; 389:2063-2075 DOI: 10.1056/NEJMoa2307980

Dr. Anjan Patel's Thoughts

Very interesting study using tarlatamab, a bispecific T-cell engager that directs T-cells to malignant cells expressing delta-like ligand 3 (DLL3).  This was a dose escalation phase II, ORR was 40% and the longevity of response in responders was impressive for this disease.   Further studies are sure to come.

BACKGROUND

Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.

METHODS

In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1.

RESULTS

Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events.

CONCLUSIONS

Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016. opens in new tab.)

Author Affiliations

From Samsung Medical Center, Sungkyunkwan University School of Medicine (M.-J.A.), and Yonsei Cancer Center, Yonsei University College of Medicine (B.C.C.), Seoul, and Seoul National University Bundang Hospital, Seongnam (J.-S.L.) — all in South Korea; Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (E.F.) and Hospital de la Santa Creu i Sant Pau (M. Majem), Barcelona, Hospital Universitari i Politecnic La Fe, Valencia (O.J.-V.), and Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc, Madrid (L.P.-A.) — all in Spain; the Department of Medical Oncology, Saint Loukas Hospital, Thessaloniki, Greece (I.K.); the Department of Respiratory Medicine, Okayama University Hospital, Okayama (K.O.), the Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa (H.I.), and Wakayama Medical University Hospital, Wakayama (H.A.) — all in Japan; Klinische Abteilung für Pneumologie, Universitätsklinikum Krems, Krems, Austria (S. Handzhiev); the Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk, Gdansk, Poland (R.D.); the Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne (J.W.), Lungen Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.), and the Translational Oncology–Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universitätsklinikum Würzburg, Würzburg (H.-D.H.) — all in Germany; Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom (F.B.); West Virginia University Health Sciences Center, Morgantown (J.B.A.); the Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands (A.-M.C.D.); Dana–Farber Cancer Institute, Harvard Medical School, Boston (J.S.); the Division of Hematology–Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (T.K.O.), and Fox Chase Cancer Center, Philadelphia (H.B.) — both in Pennsylvania; Winship Cancer Institute of Emory University, Atlanta (S.S.R.); Sarah Cannon Research Institute at Tennessee Oncology, Nashville (M.L.J.); and Amgen, Thousand Oaks, CA (S. Huang, S.M., M. Minocha, T.J., P.M., E.S.A.).

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