| Title: |
Phase Ib and Expansion Study of Gemcitabine, Nab-Paclitaxel, and Ficlatuzumab in Patients With Metastatic Pancreatic Cancer |
| Authors: |
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 |
| Contributors: |
AVEO Pharmaceuticals |
| Source: |
The Oncologist ; volume 28, issue 5, page 425-432 ; ISSN 1083-7159 1549-490X |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
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/m2 and albumin-bound paclitaxel 125 mg/m2 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, 7.6-11.4 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/oncolo/oyad002 |
| Availability: |
https://doi.org/10.1093/oncolo/oyad002; https://academic.oup.com/oncolo/article-pdf/28/5/425/50247655/oyad002.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.ECD54939 |
| Database: |
BASE |