TY - JOUR
T1 - Ramucirumab and durvalumab for previously treated, advanced non–small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma
T2 - An open-label, phase Ia/b study (JVDJ)
AU - Bang, Yung Jue
AU - Golan, Talia
AU - Dahan, Laetitia
AU - Fu, Siqing
AU - Moreno, Victor
AU - Park, Keunchil
AU - Geva, Ravit
AU - De Braud, Filippo
AU - Wainberg, Zev A.
AU - Reck, Martin
AU - Goff, Laura
AU - Laing, Naomi
AU - Mi, Gu
AU - Oliveira, Joana M.
AU - Wasserstrom, Heather
AU - Lin, Chia Chi
N1 - Publisher Copyright:
© 2020 Eli Lilly and Company
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Durvalumab
KW - Gastric/gastro-oesophageal junction adenocarcinoma
KW - Hepatocellular carcinoma
KW - Non–small-cell lung cancer
KW - Ramucirumab
UR - http://www.scopus.com/inward/record.url?scp=85089519572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089519572&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2020.06.007
DO - 10.1016/j.ejca.2020.06.007
M3 - Article
C2 - 32827847
AN - SCOPUS:85089519572
SN - 0959-8049
VL - 137
SP - 272
EP - 284
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -