Yung-Jue Bang1, Talia Golan2, Laetitia Dahan3, Siqing Fu4, Victor Moreno5, Keunchil Park6, Ravit Geva7, Filippo De Braud8, Zev A Wainberg9, Martin Reck10, Laura Goff11, Naomi Laing12, Gu Mi13, Joana M Oliveira14, Heather Wasserstrom14, Chia-Chi Lin15. 1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: bangyj@snu.ac.kr. 2. Sheba Medical Center, Tel-Aviv University, Ramat Gan, Tel Aviv, Israel. 3. Hôpital de la Timone et Aix-Marseille Université, Marseille, France. 4. The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 5. START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain. 6. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 7. Tel Aviv Sourasky Medical Center, Tel-Aviv University, Tel Aviv, Israel. 8. Department of Medical Oncology, University of Milan, Milan, Italy. 9. Medical Hematology and Oncology, University of California Los Angeles, Los Angeles, CA, USA. 10. Lungen Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. 11. Vanderbilt University Medical Center, Nashville, TN, USA. 12. AstraZeneca, Gaithersburg, MD, USA. 13. Eli Lilly and Company, Indianapolis, IN, USA. 14. Eli Lilly and Company, New York, NY, USA. 15. National Taiwan University Hospital, Taipei, Taiwan.
Abstract
BACKGROUND: Emerging evidence supports combining immune checkpoint inhibitors (ICIs) with conventional or targeted therapies to enhance ICI antitumour activity and broaden the spectrum of patients who respond to ICIs. Here, we present the safety and preliminary efficacy of ramucirumab, an anti-VEGFR2 IgG1, plus durvalumab, an anti-PD-L1 IgG1, in previously treated patients with advanced non-small-cell lung cancer (NSCLC), gastric/gastro-oesophageal junction adenocarcinoma (gastric/GEJ), or hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A 25-centre, phase Ia/b single-arm, non-randomised, multi-cohort study was undertaken in patients with advanced/metastatic disease, Eastern Cooperative Oncology Group performance status, 0-1, progression on prior therapy, no prior ramucirumab or immunotherapy and any PD-L1 status. Patients received ramucirumab (10 mg/kg) plus durvalumab (1125 mg) intravenously Q3W (NSCLC), or ramucirumab (8 mg/kg) plus durvalumab (750 mg) Q2W (gastric/GEJ, HCC). RESULTS: Phase Ia treatment was found safe for phase Ib expansion; final enrolment was NSCLC (n = 28), gastric/GEJ (n = 29), HCC (n = 28). Grade ≥3 treatment-related adverse events occurred in 32.1%, 37.9% and 42.9% of patients, respectively. The most common were fatigue (35.7%), hypertension (34.5%) and diarrhoea (28.6%), respectively. Two patients died owing to an adverse event; one was treatment-related (hepatitis acute, HCC cohort). Objective response rate was 11% for NSCLC and HCC and 21% for gastric/GEJ. Median progression-free survival and overall survival were, respectively, 2.7 and 11 months in NSCLC; 2.6 and 12.4 months in gastric/GEJ; 4.4 and 10.7 months in HCC, with more prolonged survival in patients with high PD-L1 expression. CONCLUSION: Ramucirumab/durvalumab exhibited manageable safety. The combination showed antitumour activity in all cohorts, particularly in patients with high PD-L1 expression.
BACKGROUND: Emerging evidence supports combining immune checkpoint inhibitors (ICIs) with conventional or targeted therapies to enhance ICI antitumour activity and broaden the spectrum of patients who respond to ICIs. Here, we present the safety and preliminary efficacy of ramucirumab, an anti-VEGFR2 IgG1, plus durvalumab, an anti-PD-L1 IgG1, in previously treated patients with advanced non-small-cell lung cancer (NSCLC), gastric/gastro-oesophageal junction adenocarcinoma (gastric/GEJ), or hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A 25-centre, phase Ia/b single-arm, non-randomised, multi-cohort study was undertaken in patients with advanced/metastatic disease, Eastern Cooperative Oncology Group performance status, 0-1, progression on prior therapy, no prior ramucirumab or immunotherapy and any PD-L1 status. Patients received ramucirumab (10 mg/kg) plus durvalumab (1125 mg) intravenously Q3W (NSCLC), or ramucirumab (8 mg/kg) plus durvalumab (750 mg) Q2W (gastric/GEJ, HCC). RESULTS: Phase Ia treatment was found safe for phase Ib expansion; final enrolment was NSCLC (n = 28), gastric/GEJ (n = 29), HCC (n = 28). Grade ≥3 treatment-related adverse events occurred in 32.1%, 37.9% and 42.9% of patients, respectively. The most common were fatigue (35.7%), hypertension (34.5%) and diarrhoea (28.6%), respectively. Two patientsdied owing to an adverse event; one was treatment-related (hepatitis acute, HCC cohort). Objective response rate was 11% for NSCLC and HCC and 21% for gastric/GEJ. Median progression-free survival and overall survival were, respectively, 2.7 and 11 months in NSCLC; 2.6 and 12.4 months in gastric/GEJ; 4.4 and 10.7 months in HCC, with more prolonged survival in patients with high PD-L1 expression. CONCLUSION:Ramucirumab/durvalumab exhibited manageable safety. The combination showed antitumour activity in all cohorts, particularly in patients with high PD-L1 expression.
Authors: Ioannis A Ziogas; Alexandros P Evangeliou; Lipika Goyal; Georgios Tsoulfas; Dimitrios Giannis; Muhammad H Hayat; Konstantinos S Mylonas; Samer Tohme; David A Geller; Nahel Elias Journal: Oncologist Date: 2021-01-02
Authors: Claudia A M Fulgenzi; Thomas Talbot; Sam M Murray; Marianna Silletta; Bruno Vincenzi; Alessio Cortellini; David J Pinato Journal: Curr Treat Options Oncol Date: 2021-08-23