Phase I study of the anti-α5β1 monoclonal antibody MINT1526A with or without bevacizumab in patients with advanced solid tumors

Purpose MINT1526A is a monoclonal antibody that blocks the interaction of integrin alpha 5 beta 1 (α5β1) with its extracellular matrix ligands. This phase I study evaluated the safety and pharmacokinetics of MINT1526A with or without bevacizumab in patients with advanced solid tumors. Methods MINT15...

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Published in:Cancer chemotherapy and pharmacology Vol. 82; no. 2; pp. 339 - 351
Main Authors: Weekes, Colin D., Rosen, Lee S., Capasso, Anna, Wong, Kit Man, Ye, Weilan, Anderson, Maria, McCall, Bruce, Fredrickson, Jill, Wakshull, Eric, Eppler, Steve, Shon-Nguyen, Quyen, Desai, Rupal, Huseni, Mahrukh, Hegde, Priti S., Pourmohamad, Tony, Rhee, Ina, Bessudo, Alberto
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2018
Springer Nature B.V
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological - administration & dosage
Antineoplastic Agents, Immunological - immunology
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - immunology
Bevacizumab
Bevacizumab - administration & dosage
Bevacizumab - immunology
Cancer Research
Dehydration
Diarrhea
Dose-Response Relationship, Drug
Extracellular matrix
Fatigue
Female
Headache
Hepatocellular carcinoma
Humans
Immunotherapy
Integrin alpha5beta1 - antagonists & inhibitors
Integrin alpha5beta1 - immunology
Liver cancer
Male
Medicine
Medicine & Public Health
Middle Aged
Monoclonal antibodies
Monocytes
Nausea
Neoplasms - drug therapy
Neoplasms - immunology
Oncology
Original Article
Pain
Pharmacokinetics
Pharmacology/Toxicology
Solid tumors
Targeted cancer therapy
Thymus
Vomiting
Angiogenesis
MINT1526A
α5β1
VEGF
ISSN:0344-5704, 1432-0843, 1432-0843
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Summary:Purpose MINT1526A is a monoclonal antibody that blocks the interaction of integrin alpha 5 beta 1 (α5β1) with its extracellular matrix ligands. This phase I study evaluated the safety and pharmacokinetics of MINT1526A with or without bevacizumab in patients with advanced solid tumors. Methods MINT1526A was administered every 3 weeks (Q3W) as monotherapy (arm 1) or in combination with bevacizumab 15 mg/kg, Q3W (arm 2). Each arm included a 3 + 3 dose-escalation stage and a dose-expansion stage. Results Twenty-four patients were enrolled in arm 1 (dose range 2–30 mg/kg) and 30 patients were enrolled in arm 2 (dose range 3–15 mg/kg). Monocyte α5β1 receptor occupancy was saturated at a dose of 15 mg/kg. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached in either arm. The most common adverse events, regardless of causality, included abdominal pain (25%), diarrhea (25%), nausea (21%), vomiting (21%), and fatigue (21%) in arm 1 and nausea (40%), fatigue (33%), vomiting (30%), dehydration (30%), headache (30%), and hypertension (30%) in arm 2. No grade ≥ 3 bleeding events were observed in either arm. No confirmed partial responses (PR) were observed in arm 1. In arm 2, one patient with thymic carcinoma experienced a confirmed PR and two patients with hepatocellular carcinoma (HCC) experienced durable minor radiographic responses. Conclusions MINT1526A, with or without bevacizumab, was well-tolerated. Preliminary evidence of combination efficacy, including in patients with HCC, was observed, but cannot be distinguished from bevacizumab monotherapy in this phase I study.
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ISSN:0344-5704
1432-0843
1432-0843
DOI:10.1007/s00280-018-3622-8