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

Author(s): Charles M. Rudin, MD, PhD1; Melissa L. Johnson, MD2; Luis Paz-Ares, MD, PhD3; Makoto Nishio, MD, PhD4; Christine L. Hann, MD, PhD5; Nicolas Girard, MD, PhD6; Pedro Rocha, MD, PhD7; Hidetoshi Hayashi, MD, PhD8; Tetsuya Sakai, MD, PhD9; Yu Jung Kim, MD, PhD10; Haichuan Hu, MD, PhD11; Meng Qian, PhD12; Jasmeet Singh, MD, MPHA12; Juliette Godard, PharmD13; Mei Tang, MD, PhD12; Myung-Ju Ahn, MD14;
Source: DOI: 10.1200/JCO-25-02142
Original Article
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A B7 homolog 3–directed antibody-drug conjugate, demonstrated an overall response rate of 48.2%, with a median duration of response of 5.3 months, and a median progression-free survival of 4.9 months. The 9-month overall survival estimate was 59.1%. This represents another ADC with promising activity, although interstitial lung disease remains a concern, occurring in approximately 12% of patients.

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.

Author Affiliations

1Memorial Sloan Kettering Cancer Center, New York, NY; 2Sarah Cannon Research Institute, Nashville, TN; 3Hospital Universitario 12 de Octubre, Madrid, Spain; 4The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; 5Sidney Kimmel Comprehensive Cancer Center Johns Hopkins, Baltimore, MD; 6Institut Curie, Paris, France; 7Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain; 8Kindai University, Osaka, Japan; 9National Cancer Center Hospital East, Kashiwa, Japan; 10Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea; 11Merck & Co, Inc, Rahway, NJ; 12Daiichi Sankyo, Inc, Basking Ridge, NJ; 13Daiichi Sankyo SAS, Paris, France; 14Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

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