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A phase 2 study of ontuxizumab, a monoclonal antibody targeting endosialin, in metastatic melanoma

  • PHASE II STUDIES
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Summary

Objectives Ontuxizumab (MORAB-004) is a first-in-class monoclonal antibody that interferes with endosialin function, which is important in tumor stromal cell function, angiogenesis, and tumor growth. This Phase 2 study evaluated the 24-week progression-free survival (PFS) value, pharmacokinetics, and tolerability of 2 doses of ontuxizumab in patients with metastatic melanoma. Patients and methods Patients with metastatic melanoma and disease progression after receiving at least 1 prior systemic treatment were randomized to receive ontuxizumab (2 or 4 mg/kg) weekly, without dose change, until disease progression. Results Seventy-six patients received at least 1 dose of ontuxizumab (40 received 2 mg/kg, 36 received 4 mg/kg). The primary endpoint, 24-week PFS value, was 11.4% (95% Confidence Interval [CI]: 5.3%–19.9%) for all patients (13.5% for 2 mg/kg and 8.9% for 4 mg/kg). The median PFS for all patients was 8.3 weeks (95% CI: 8.1–12.3 weeks). One patient receiving 4 mg/kg had a partial response, as measured by Response Evaluation Criteria in Solid Tumors v1.1. Twenty-seven of 66 response evaluable patients (40.9%) had stable disease. The median overall survival was 31.0 weeks (95% CI: 28.3–44.0 weeks). The most common adverse events overall were headache (55.3%), fatigue (48.7%), chills (42.1%), and nausea (36.8%), mostly grade 1 or 2. Conclusions Ontuxizumab at both doses was well tolerated. The 24-week PFS value was 11.4% among all ontuxizumab-treated patients. The overall response rate was 3.1% at the 4 mg/kg dose, with clinical benefit achieved in 42.4% of response evaluable patients. Efficacy of single-agent ontuxizumab at these doses in melanoma was low.

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Acknowledgements

Medical writing assistance was provided by M.L. Skoglund, PhD; Healthcare Consulting.

Funding

This study was funded by Morphotek, Inc.

Author information

Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Sandra P. D’Angelo

  2. Weill Cornell Medical College, New York, NY, USA

    Sandra P. D’Angelo

  3. The Angeles Clinic and Research Institute, Los Angeles, CA, USA

    Omid A. Hamid

  4. University of Pittsburgh, Pittsburgh, PA, USA

    Ahmad Tarhini

  5. Universitätsklinikum Essen, Essen, Germany

    Dirk Schadendorf

  6. University of California, Los Angeles, CA, USA

    Bartosz Chmielowski

  7. University of North Carolina, Chapel Hill, NC, USA

    Frances A. Collichio

  8. New York University, Lake Success, NY, USA

    Anna C. Pavlick

  9. University of Colorado Cancer Center, Aurora, CO, USA

    Karl D. Lewis

  10. Morphotek, Inc., Exton, PA, USA

    Susan C. Weil, John Heyburn, Charles Schweizer & Daniel J. O’Shannessy

  11. Columbia University Medical Center, 177 Ft Washington Avenue, New York, NY, 10032, USA

    Richard D. Carvajal

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Corresponding author

Correspondence to Richard D. Carvajal.

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Conflict of interest

Sandra D’Angelo has no conflicts of interest to report.

Omid A. Hamid is consulting for Amgen, Novartis, Roche, BMS and Merck.

Ahmad Tarhini has received a grant from Morphotek, BMS and Merck, is consulting for BMS and Merck.

Dirk Schadendorf has board membership and consulting GSK, Roche, BMS, Amgen, Novartis, Merck, Pfizer, Astra Zeneca. He also has Grant support from BMS and MSD/Merck.

Bartosz Chmielowski is consulting Genentech, Amgen, BMS, Astella, Merck, Eisai, Immunocore, Lilly; he received payment for lectures and travel from Genetech, Janseen and Amgen.

Frances A. Collichio has received grant support from Morphotek, Amgen, Novartis, Vascular Biogenics Ltd., GSK, Amgen, Mayo Phase II and is consulting for Amgen.

Anna C. Pavlick is consulting for BMS and Merck and development of educational presentations from Novartis.

Karl D. Lewis has received grant support from Morphotek.

Susan C. Weil is employed by Morphotek.

John Heyburn was employed by Morphotek.

Charles Schweizer was employed by Morphotek.

Daniel J. O’Shannessy was employed by Morphotek.

Richard Carvajal is consulting for AstraZeneca, BMS, Iconic Therapeutics, Janssen, Merck, Novartis, Roche/Genentech, Thomson Reuters and is board member of Aura Biosciences, Chimeron, Rgenix.

Ethical approval

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

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

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D’Angelo, S.P., Hamid, O.A., Tarhini, A. et al. A phase 2 study of ontuxizumab, a monoclonal antibody targeting endosialin, in metastatic melanoma. Invest New Drugs 36, 103–113 (2018). https://doi.org/10.1007/s10637-017-0530-4

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  • DOI: https://doi.org/10.1007/s10637-017-0530-4

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