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- Title
Safety and Efficacy of Andecaliximab (GS‐5745) Plus Gemcitabine and Nab‐Paclitaxel in Patients with Advanced Pancreatic Adenocarcinoma: Results from a Phase I Study.
- Authors
Bendell, Johanna; Sharma, Sunil; Patel, Manish R.; Windsor, Kevin S.; Wainberg, Zev A.; Gordon, Michael; Chaves, Jorge; Berlin, Jordan; Brachmann, Carrie Baker; Zavodovskaya, Marianna; Liu, JieJane; Thai, Dung; Bhargava, Pankaj; Shah, Manish A.; Khan, Saad A.; Starodub, Alexander
- Abstract
Background: Matrix metalloproteinase 9 (MMP9) expression in the tumor microenvironment is implicated in multiple protumorigenic processes. Andecaliximab (GS‐5745), a monoclonal antibody targeting MMP9 with high affinity and selectivity, was evaluated in combination with gemcitabine and nab‐paclitaxel in patients with advanced pancreatic adenocarcinoma. Patients and Methods: This phase I study was completed in two parts: part A was a dose‐finding, monotherapy phase that enrolled patients with advanced solid tumors, and part B examined andecaliximab in combination with chemotherapy in specific patient cohorts. In the cohort of patients with pancreatic adenocarcinoma (n = 36), andecaliximab 800 mg every 2 weeks was administered in combination with gemcitabine and nab‐paclitaxel. Patients were treated until unacceptable toxicity, withdrawal of consent, disease progression, or death. Efficacy, safety, and biomarker assessments were performed. Results: Andecaliximab combined with gemcitabine and nab‐paclitaxel appeared to be well tolerated and did not demonstrate any unusual toxicities in patients with pancreatic adenocarcinoma. The most common treatment‐emergent adverse events were fatigue (75.0%), alopecia (55.6%), peripheral edema (55.6%), and nausea (50.0%). Median progression‐free survival was 7.8 months (90% confidence interval, 6.9−11.0) with an objective response rate of 44.4% and median duration of response of 7.6 months. Maximal andecaliximab target binding, defined as undetectable, andecaliximab‐free MMP9 in plasma, was observed. Conclusion: Andecaliximab in combination with gemcitabine and nab‐paclitaxel demonstrates a favorable safety profile and clinical activity in patients with advanced pancreatic adenocarcinoma. Implications for Practice: The combination of andecaliximab, a novel, first‐in‐class inhibitor of matrix metalloproteinase 9, with gemcitabine and nab‐paclitaxel in patients with advanced pancreatic adenocarcinoma provided a median progression‐free survival of 7.8 months and objective response rate of 44.4%. The majority of systemic biomarkers related to matrix metalloproteinase 9 activity and immune suppression increased at 2 months, whereas biomarkers related to tumor burden decreased. Although this study demonstrates promising results with andecaliximab plus chemotherapy in patients with advanced pancreatic adenocarcinoma, andecaliximab was not associated with a survival benefit in a phase III study in patients with advanced gastric/gastroesophageal junction carcinoma. This article presents the results of a phase I study evaluating the safety and efficacy of andecaliximab in advanced pancreatic adenocarcinoma.
- Subjects
THERAPEUTIC use of monoclonal antibodies; THERAPEUTIC use of antimetabolites; ADENOCARCINOMA; BIOMARKERS; COMBINATION drug therapy; CLINICAL trials; DRUG side effects; GENE expression; IMMUNOHISTOCHEMISTRY; MONOCLONAL antibodies; PACLITAXEL; PANCREATIC tumors; SURVIVAL; MATRIX metalloproteinases
- Publication
Oncologist, 2020, Vol 25, Issue 11, p954
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2020-0474