학술논문
Phase Ib and Expansion Study of Gemcitabine, Nab-Paclitaxel, and Ficlatuzumab in Patients With Metastatic Pancreatic Cancer
Original Article
Original Article
Document Type
Report
Author
Perez, Kimberly; Chiarella, Anna M.; Cleary, James M.; Horick, Nora; Weekes, Colin; Abrams, Thomas; Blaszkowsky, Lawrence; Enzinger, Peter; Giannakis, Marios; Goyal, Lipika; Meyerhardt, Jeffrey A.; Rubinson, Douglas; Yurgelun, Matthew B.; Goessling, Wolfram; Giantonio, Bruce J.; Brais, Lauren; Germon, Victoria; Stonely, Danielle; Raghavan, Srivatsan; Bakir, Basil; Das, Koushik; Pitarresi, Jason R.; Aguirre, Andrew J.; Needle, Michael; Rustgi, Anil K.; Wolpin, Brian M.
Source
The Oncologist. May 2023, Vol. 28 Issue 5, p425, 8 p.
Subject
Language
English
ISSN
1083-7159
Abstract
Implications for Practice Dysregulation of the hepatocyte growth factor (HGF)/c-Met signaling pathway can lead to aberrant cell proliferation, drug resistance, and promotion of cell migration and invasion. In pre-clinical pancreatic [...]
Background: In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of hepatocyte growth factor (HGF) signaling using ficlatuzumab, a recombinant humanized anti-HGF antibody, and gemcitabine reduced tumor burden. Methods: Patients with previously untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3 + 3 design of 2 dose cohorts of ficlatuzumab 10 and 20 mg/kg administered intravenously every other week with gemcitabine 1000 mg/[m.sup.2] and albumin-bound paclitaxel 125 mg/[m.sup.2] given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose of the combination. Results: Twenty-six patients (sex, 12 male:14 female; median age, 68 years [range, 49-83 years]) were enrolled, 22 patients were evaluable. No dose-limiting toxicities were identified (N = 7 pts) and ficlatuzumab at 20 mg/kg was chosen as the maximum tolerated dose. Among the 21 patients treated at the MTD, best response by RECISTv1.1: 6 (29%) partial response, 12 (57%) stable disease, 1 (5%) progressive disease, and 2 (9%) not evaluable. Median progression-free survival and overall survival times were 11.0 months (95% CI, 76- 11.4 months) and 16.2 months (95% CI, 9.1 months to not reached), respectively. Toxicities attributed to ficlatuzumab included hypoalbuminemia (grade 3, 16%; any grade, 52%) and edema (grade 3, 8%; any grade, 48%). Immunohistochemistry for c-Met pathway activation demonstrated higher tumor cell p-Met levels in patients who experienced response to therapy. Conclusion: In this phase Ib trial, ficlatuzumab, gemcitabine, and albumin-bound paclitaxel were associated with durable treatment responses and increased rates of hypoalbuminemia and edema. Key words: phase Ib clinical trial; gemcitabine; nao-paclitaxel; ficlatuzumab; metastatic pancreatic cancer.
Background: In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of hepatocyte growth factor (HGF) signaling using ficlatuzumab, a recombinant humanized anti-HGF antibody, and gemcitabine reduced tumor burden. Methods: Patients with previously untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3 + 3 design of 2 dose cohorts of ficlatuzumab 10 and 20 mg/kg administered intravenously every other week with gemcitabine 1000 mg/[m.sup.2] and albumin-bound paclitaxel 125 mg/[m.sup.2] given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose of the combination. Results: Twenty-six patients (sex, 12 male:14 female; median age, 68 years [range, 49-83 years]) were enrolled, 22 patients were evaluable. No dose-limiting toxicities were identified (N = 7 pts) and ficlatuzumab at 20 mg/kg was chosen as the maximum tolerated dose. Among the 21 patients treated at the MTD, best response by RECISTv1.1: 6 (29%) partial response, 12 (57%) stable disease, 1 (5%) progressive disease, and 2 (9%) not evaluable. Median progression-free survival and overall survival times were 11.0 months (95% CI, 76- 11.4 months) and 16.2 months (95% CI, 9.1 months to not reached), respectively. Toxicities attributed to ficlatuzumab included hypoalbuminemia (grade 3, 16%; any grade, 52%) and edema (grade 3, 8%; any grade, 48%). Immunohistochemistry for c-Met pathway activation demonstrated higher tumor cell p-Met levels in patients who experienced response to therapy. Conclusion: In this phase Ib trial, ficlatuzumab, gemcitabine, and albumin-bound paclitaxel were associated with durable treatment responses and increased rates of hypoalbuminemia and edema. Key words: phase Ib clinical trial; gemcitabine; nao-paclitaxel; ficlatuzumab; metastatic pancreatic cancer.