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|Ref Type||Journal Article|
|Authors||Weekes CD, Rosen LS, Capasso A, Wong KM, Ye W, Anderson M, McCall B, Fredrickson J, Wakshull E, Eppler S, Shon-Nguyen Q, Desai R, Huseni M, Hegde PS, Pourmohamad T, Rhee I, Bessudo A|
|Title||Phase I study of the anti-α5β1 monoclonal antibody MINT1526A with or without bevacizumab in patients with advanced solid tumors.|
|Journal||Cancer chemotherapy and pharmacology|
|Date||2018 Jun 15|
|Abstract Text||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.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.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.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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|MINT1526A||RG-7594|MINT-1526A||MINT1526A is a monoclonal antibody against integrin alpha 5 beta 1 that blocks interaction with extracellular matrix thus potentially leads to tumor cell death (PMID: 29905898).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||thymic carcinoma||not applicable||Bevacizumab + MINT1526A||Phase I||Actionable||In a Phase I trial, MINT1526A in combination with Avastin (bevacizumab) resulted in partial response in a patient with thymic carcinoma (PMID: 29905898).||29905898|
|Unknown unknown||Advanced Solid Tumor||no benefit||MINT1526A||Phase I||Actionable||In a Phase I trial, MINT1526A monotherapy did not result in partial response in patients with advanced solid tumors (PMID: 29905898).||29905898|
|Unknown unknown||hepatocellular carcinoma||not applicable||Bevacizumab + MINT1526A||Phase I||Actionable||In a Phase I trial, MINT1526A in combination with Avastin (bevacizumab) resulted in durable minor radiographic responses in 2 patients with hepatocellular carcinoma (PMID: 29905898).||29905898|
|Unknown unknown||Advanced Solid Tumor||not applicable||Bevacizumab + MINT1526A||Phase I||Actionable||In a Phase I trial, MINT1526A in combination with Avastin (bevacizumab) resulted in 1 partial response and 2 durable minor radiographic responses in a total of 30 patients with advanced solid tumors (PMID: 29905898).||29905898|