Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial

  • J Clin Oncol. 2026 Feb;44(4):261-273. doi: 10.1200/JCO-25-02142.
Charles M Rudin  1 ,  Melissa L Johnson  2 ,  Luis Paz-Ares  3 ,  Makoto Nishio  4 ,  Christine L Hann  5 ,  Nicolas Girard  6 ,  Pedro Rocha  7 ,  Hidetoshi Hayashi  8 ,  Tetsuya Sakai  9 ,  Yu Jung Kim  10 ,  Haichuan Hu  11 ,  Meng Qian  12 ,  Jasmeet Singh  12 ,  Juliette Godard  13 ,  Mei Tang  12 ,  Myung-Ju Ahn  14
Affiliations
  • 1. Memorial Sloan Kettering Cancer Center, New York, NY.
  • 2. Sarah Cannon Research Institute, Nashville, TN.
  • 3. Hospital Universitario 12 de Octubre, Madrid, Spain.
  • 4. The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 5. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
  • 6. Institut Curie, Paris, France.
  • 7. Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • 8. Kindai University, Osaka, Japan.
  • 9. National Cancer Center Hospital East, Kashiwa, Japan.
  • 10. Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
  • 11. Merck & Co, Inc, Rahway, NJ.
  • 12. Daiichi Sankyo, Inc, Basking Ridge, NJ.
  • 13. Daiichi Sankyo SAS, Paris, France.
  • 14. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
PMID: 41086386 DOI: 10.1200/JCO-25-02142
Abstract

Purpose: Treatment options for patients with recurrent or progressive extensive-stage small cell lung Cancer (ES-SCLC) are limited. This phase II trial evaluated the efficacy and safety of ifinatamab deruxtecan (I-DXd), a B7 homolog 3-directed antibody-drug conjugate, in patients with previously treated ES-SCLC.

Methods: Patients were randomly assigned to receive I-DXd 8 or 12 mg/kg intravenously once every 3 weeks in part 1 (dose optimization) and received I-DXd 12 mg/kg in part 2 (extension). The primary end point was objective response rate (ORR) by blinded independent central review per RECIST, version 1.1.

Results: Overall, 183 patients received I-DXd: 88 in part 1 (8 mg/kg, n = 46; 12 mg/kg, n = 42) and 95 in part 2. The median number of previous lines of treatment was two. In the total 12-mg/kg group from parts 1 and 2 (n = 137), the confirmed ORR was 48.2% (95% CI, 39.6 to 56.9), median duration of response was 5.3 (95% CI, 4.0 to 6.5) months, median time to response was 1.4 (range, 1.0-8.1) months, median progression-free survival was 4.9 (95% CI, 4.2 to 5.5) months, and the 9-month overall survival estimate was 59.1%. Any-grade treatment-related adverse events (TRAEs) occurred in 89.8% of patients (grade ≥3, 36.5%). The most common TRAEs were nausea (43.1%), anemia (34.3%), and neutropenia (34.3%). TRAEs associated with treatment discontinuation and death were reported in 9.5% and 4.4% of patients, respectively. Treatment-related interstitial lung disease (ILD) as determined by the ILD adjudication committee was reported in 12.4% of patients (grade ≥3, 4.4%).

Conclusion: I-DXd 12 mg/kg once every 3 weeks showed promising efficacy in patients with previously treated ES-SCLC. The observed safety profile was consistent with previous reports, with no new safety signals identified.

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