Luis Paz-Ares1, Tae Min Kim2, David Vicente3, Enriqueta Felip4, Dae Ho Lee5, Ki Hyeong Lee6, Chia-Chi Lin7, Maria Jose Flor8, Massimo Di Nicola9, Rosa Maria Alvarez10, Isabelle Dussault11, Christoph Helwig12, Laureen S Ojalvo11, James L Gulley13, Byoung Chul Cho14. 1. HI2O-CNIO Haematological Malignancies Clinical Research Unit (Hospital Universitario 12 de Octubre-CNIO), Universidad Complutense & Ciberonc, Madrid, Spain. Electronic address: lpazares@seom.org. 2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 3. Department of Clinical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain. 4. Medical Oncology Department, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain. 5. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 6. Deparment of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea. 7. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. 8. Servicio de Oncología Médica, Hospital Universitario Virgen del Rocío, Seville, Spain. 9. Unit of Immunotherapy and Anticancer Innovative Therapeutics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 10. Department of Medical Oncology, Gregorio Marañon Hospital, Madrid, Spain. 11. EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts; a business of Merck KGaA, Darmstadt, Germany; Merck KGaA, Darmstadt, Germany. 12. Merck KGaA, Darmstadt, Germany. 13. Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 14. Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Abstract
INTRODUCTION: The safety and efficacy of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β) receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1), was evaluated in patients with advanced NSCLC. METHODS: This expansion cohort of NCT02517398, an ongoing, phase 1, open-label trial, includes 80 patients with advanced NSCLC that progressed after platinum doublet therapy or after platinum-based adjuvant or neoadjuvant treatment and those who also have not received previous immunotherapy. Patients were randomized at a one-to-one ratio to receive either bintrafusp alfa 500 mg or the recommended phase 2 dosage of 1200 mg every 2 weeks. The primary end point was the best overall response (by Response Evaluation Criteria in Solid Tumors 1.1 as adjudicated by independent review committee) and was assessed by the objective response rate (ORR). RESULTS: A total of 80 patients were randomized to receive bintrafusp alfa 500 or 1200 mg (n = 40 each). Median follow-up was 51.9 weeks (IQR, 19.6-74.0). The ORR in all patients was 21.3% (17 of 80). The ORR was 17.5% (seven of 40) and 25.0% (10 of 40) for the 500 mg dose and the 1200 mg dose (recommended phase 2 dose), respectively. At the 1200 mg dose, patients with PD-L1-positive and PD-L1-high (≥80% expression on tumor cells) had ORRs of 36.0% (10 of 27) and 85.7% (six of seven), respectively. Treatment-related adverse events occurred in 55 of the 80 patients (69%) and were graded as greater than or equal to 3 in 23 of the 80 patients (29%). Of the 80 patients, eight (10%) had a treatment-related adverse event that led to treatment discontinuation; no treatment-related deaths occurred. CONCLUSIONS: Bintrafusp alfa had encouraging efficacy and manageable tolerability in patients with NSCLC previously treated with platinum.
INTRODUCTION: The safety and efficacy of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β) receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1), was evaluated in patients with advanced NSCLC. METHODS: This expansion cohort of NCT02517398, an ongoing, phase 1, open-label trial, includes 80 patients with advanced NSCLC that progressed after platinum doublet therapy or after platinum-based adjuvant or neoadjuvant treatment and those who also have not received previous immunotherapy. Patients were randomized at a one-to-one ratio to receive either bintrafusp alfa 500 mg or the recommended phase 2 dosage of 1200 mg every 2 weeks. The primary end point was the best overall response (by Response Evaluation Criteria in Solid Tumors 1.1 as adjudicated by independent review committee) and was assessed by the objective response rate (ORR). RESULTS: A total of 80 patients were randomized to receive bintrafusp alfa 500 or 1200 mg (n = 40 each). Median follow-up was 51.9 weeks (IQR, 19.6-74.0). The ORR in all patients was 21.3% (17 of 80). The ORR was 17.5% (seven of 40) and 25.0% (10 of 40) for the 500 mg dose and the 1200 mg dose (recommended phase 2 dose), respectively. At the 1200 mg dose, patients with PD-L1-positive and PD-L1-high (≥80% expression on tumor cells) had ORRs of 36.0% (10 of 27) and 85.7% (six of seven), respectively. Treatment-related adverse events occurred in 55 of the 80 patients (69%) and were graded as greater than or equal to 3 in 23 of the 80 patients (29%). Of the 80 patients, eight (10%) had a treatment-related adverse event that led to treatment discontinuation; no treatment-related deaths occurred. CONCLUSIONS: Bintrafusp alfa had encouraging efficacy and manageable tolerability in patients with NSCLC previously treated with platinum.
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