OBJECTIVE: • To evaluate the efficacy and safety of single-agent AMG 102, an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), in renal cell carcinoma (RCC). PATIENTS AND METHODS: • This open-label phase II study included patients ≥ 18 years old with histologically confirmed, advanced or metastatic RCC (mRCC) and Eastern Cooperative Oncology Group performance status 0 to 2. AMG 102 was administered i.v. at 10 or 20 mg/kg once every 2 weeks. • A two-stage design was used at each dose level and the primary endpoint was objective best confirmed response (by Response Evaluation Criteria in Solid Tumours) at any time. RESULTS: • Sixty-one patients with mRCC enrolled and received AMG 102 (40 at 10 mg/kg; 21 at 20 mg/kg). Overall, 70.5% were men, median age was 59 years (range, 39 to 84 years), and 92% had received previous anti-vascular endothelial growth factor therapy. RCC histologies were: clear cell (75.4%), papillary (11.5%), chromophobe (4.9%) and unclassified (8.2%). • One confirmed partial response occurred at 10 mg/kg, maintained for over 2.5 years; 26 patients (43%) had stable disease, 10 (16%) for ≥ 32 weeks. The median profression-free survival was 3.7 months at 10 mg/kg and 2.0 months at 20 mg/kg. The commonest adverse events were oedema (45.9%), fatigue (37.7%) and nausea (27.9%). Grade 3 or 4 adverse events occurred in 33% of patients, the most common being oedema (9.8%). • Baseline levels of plasma HGF/SF and soluble c-Met as well as archival-tumour c-Met did not correlate with measures of efficacy. CONCLUSION: • Single-agent AMG 102 was tolerable, but it is unclear if AMG 102 was growth inhibitory in this population of patients with mRCC.
OBJECTIVE: • To evaluate the efficacy and safety of single-agent AMG 102, an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), in renal cell carcinoma (RCC). PATIENTS AND METHODS: • This open-label phase II study included patients ≥ 18 years old with histologically confirmed, advanced or metastatic RCC (mRCC) and Eastern Cooperative Oncology Group performance status 0 to 2. AMG 102 was administered i.v. at 10 or 20 mg/kg once every 2 weeks. • A two-stage design was used at each dose level and the primary endpoint was objective best confirmed response (by Response Evaluation Criteria in Solid Tumours) at any time. RESULTS: • Sixty-one patients with mRCC enrolled and received AMG 102 (40 at 10 mg/kg; 21 at 20 mg/kg). Overall, 70.5% were men, median age was 59 years (range, 39 to 84 years), and 92% had received previous anti-vascular endothelial growth factor therapy. RCC histologies were: clear cell (75.4%), papillary (11.5%), chromophobe (4.9%) and unclassified (8.2%). • One confirmed partial response occurred at 10 mg/kg, maintained for over 2.5 years; 26 patients (43%) had stable disease, 10 (16%) for ≥ 32 weeks. The median profression-free survival was 3.7 months at 10 mg/kg and 2.0 months at 20 mg/kg. The commonest adverse events were oedema (45.9%), fatigue (37.7%) and nausea (27.9%). Grade 3 or 4 adverse events occurred in 33% of patients, the most common being oedema (9.8%). • Baseline levels of plasma HGF/SF and soluble c-Met as well as archival-tumourc-Met did not correlate with measures of efficacy. CONCLUSION: • Single-agent AMG 102 was tolerable, but it is unclear if AMG 102 was growth inhibitory in this population of patients with mRCC.
Authors: G T Gibney; S A Aziz; R L Camp; P Conrad; B E Schwartz; C R Chen; W K Kelly; H M Kluger Journal: Ann Oncol Date: 2012-09-28 Impact factor: 32.976
Authors: Zhenfu Han; Peter K W Harris; Darin E Jones; Ryan Chugani; Tommy Kim; Manjula Agarwal; Wei Shen; Scott A Wildman; James W Janetka Journal: ACS Med Chem Lett Date: 2014-10-09 Impact factor: 4.345
Authors: David S Hong; Patricia LoRusso; Omid Hamid; Filip Janku; Muaiad Kittaneh; Daniel V T Catenacci; Emily Chan; Tanios Bekaii-Saab; Shirish M Gadgeel; Robert D Loberg; Benny M Amore; Yuying C Hwang; Rui Tang; Gataree Ngarmchamnanrith; Eunice L Kwak Journal: Clin Cancer Res Date: 2018-11-13 Impact factor: 12.531
Authors: Conor A Bradley; Manuel Salto-Tellez; Pierre Laurent-Puig; Alberto Bardelli; Christian Rolfo; Josep Tabernero; Hajrah A Khawaja; Mark Lawler; Patrick G Johnston; Sandra Van Schaeybroeck Journal: Nat Rev Clin Oncol Date: 2017-04-04 Impact factor: 66.675