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

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Abstract

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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Acknowledgements

The authors wish many thanks to all of the patients and the investigators who participated in this study. Editing and writing support was provided by A. Daisy Goodrich (Genentech, Inc., South San Francisco, CA, USA) and was funded by Genentech, Inc.

Funding

This work was supported by Genentech, Inc., South San Francisco, CA.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Massachusetts General Hospital, 55 Fruit St, Yawkey 7E, Boston, MA, 02114, USA

    Colin D. Weekes

  2. Division of Hematology-Oncology, University of California-Los Angeles, Santa Monica, CA, USA

    Lee S. Rosen

  3. Division of Medical Oncology, University of Colorado School of Medicine and Developmental Therapeutics Program, University of Colorado Cancer Center, Aurora, CO, USA

    Anna Capasso

  4. Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA, USA

    Kit Man Wong

  5. Genentech, Inc., South San Francisco, CA, USA

    Weilan Ye, Maria Anderson, Bruce McCall, Jill Fredrickson, Eric Wakshull, Steve Eppler, Quyen Shon-Nguyen, Rupal Desai, Mahrukh Huseni, Priti S. Hegde, Tony Pourmohamad & Ina Rhee

  6. California Cancer Associates for Research & Excellence, Encinitas, CA, USA

    Alberto Bessudo

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  1. Colin D. Weekes
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Corresponding author

Correspondence to Colin D. Weekes.

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Conflict of interest

C.D. Weekes, A. Capasso, K.M. Wong, and A. Bessudo have no disclosures. L.S. Rosen is affiliated with institution that received research funding from Genentech. W. Ye, M. Anderson, B. McCall, J. Fredrickson, E. Wakshull, S. Eppler, Q. Shon-Nguyen, R. Desai, M. Huseni, P.S. Hegde, T. Pourmohamad, and I. Rhee are employees of Genentech, Inc., and shareholders of Roche.

Research involving human participants and/or animals

This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all individual participants included in the study.

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Weekes, C.D., Rosen, L.S., Capasso, A. et al. Phase I study of the anti-α5β1 monoclonal antibody MINT1526A with or without bevacizumab in patients with advanced solid tumors. Cancer Chemother Pharmacol 82, 339–351 (2018). https://doi.org/10.1007/s00280-018-3622-8

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