作者: Aguirre, Andrew J ; Rustgi, Anil K ; Germon, Victoria ; Enzinger, Peter ; Bakir, Basil ; Raghavan, Srivatsan ; Goyal, Lipika ; Giannakis, Marios ; Weekes, Colin ; Giantonio, Bruce J ; Das, Koushik ; Needle, Michael ; Abrams, Thomas ; Stonely, Danielle ; Yurgelun, Matthew B ; Pitarresi, Jason R ; Chiarella, Anna M ; Perez, Kimberly ; Rubinson, Douglas ; Goessling, Wolfram ; Blaszkowsky, Lawrence ; Horick, Nora ; Meyerhardt, Jeffrey A ; Brais, Lauren ; Wolpin, Brian M ; Cleary, James M

Abstract:

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.

2022-12-01·Dermatologic therapy

Omalizumab as a corticosteroid‐sparing agent in the treatment of bullous pemphigoid

Article

作者: Brazzelli, Valeria ; Vassallo, Camilla ; De Amici, Mara ; Barruscotti, Stefania ; Somenzi, Anita

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.

2021-09-01·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology2区 · 医学

Characteristics of patients with chronic spontaneous urticaria showing early and complete responses to omalizumab

2区 · 医学

Article

作者: Fu, Ko-Ting ; Cho, Yung-Tsu ; Chu, Chia-Yu ; Yang, Che-Wen

Chronic spontaneous urticaria (CSU) affects a large number of people, affecting quality of life and daily activities.Omalizumab, a recombinant humanized anti-IgE (IgE) monoclonal antibody, has been found to have efficacy in treating CSU, which might be through its ability to reduce the level of free IgE and subsequently reduce the expression of high-affinity receptor for the Fc region of IgE (FcεRI) on mast cells and basophils.To better figure out these rapid omalizumab responders, a study was performed in a tertiary referral medical center in Northern Taiwan (institutional review board number, 201707023MIFB) to recruit patients with CSU from Dec. 2017 to Feb. 2019.Baseline IgE levels were elevated in 12 of the patients (63.2%), with an average value of 357.1 IU/mL.The expressions of FcεRI and CD63 on patients' basophils were evaluated using flow cytometry.The levels of LTC4 released by Ku812 cells remained stationary when being treated with the patients' sera before and after omalizumab treatment.In conclusion, the characteristics of early complete omalizumab responders were found in CSU.These patients reveal lowest basophil FcεRI expressions after omalizumab treatment.They have less activated basophils and less serum releasibility on Ku812 cells at the baseline.These findings may help identify patients who may benefit most from omalizumab.

100 项与奥马珠单抗生物类似药（上海泰因）相关的药物交易

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