An open-label, dose-escalation phase I study of anti-TYRP1 monoclonal antibody IMC-20D7S for patients with relapsed or refractory melanoma Journal Article
| Authors: | Khalil, D. N.; Postow, M. A.; Ibrahim, N.; Ludwig, D. L.; Cosaert, J.; Kambhampati, S. R. P.; Tang, S.; Grebennik, D.; Kauh, J. S. W.; Lenz, H. J.; Flaherty, K. T.; Hodi, F. S.; Lawrence, D. P.; Wolchok, J. D. |
| Article Title: | An open-label, dose-escalation phase I study of anti-TYRP1 monoclonal antibody IMC-20D7S for patients with relapsed or refractory melanoma |
| Abstract: | Purpose: Tyrosinase-related protein-1 (TYRP1) is a transmembrane glycoprotein that is specifically expressed in melanocytes and melanoma cells. Preclinical data suggest that mAbs targeting TYRP1 confer antimelanoma activity. IMC-20D7S is a recombinant human IgG1 mAb targeting TYRP1. Here, we report the first-in-human phase I/Ib trial of IMC-20D7S. Experimental Design: Theprimaryobjectiveofthisstudywasto establish the safety profile and the MTD of IMC-20D7S. Patients with advanced melanoma who progressed after or during at least one line of treatment or for whom standard therapy was not indicated enrolled in this standard 3 + 3 dose-escalation, open-label study. IMC-20D7S was administered intravenously every 2 or 3 weeks. Results: Twenty-seven patients were enrolled. The most common adverse events were fatigue and constipation experienced by nine (33%) and eight (30%) patients, respectively. There were no serious adverse events related to treatment, no discontinuations of treatment due to adverse events, and no treatment-related deaths. Given the absence of dose-limiting toxicities, an MTD was not defined, but a provisional MTD was established at the 20 mg/kg every 2-week dose based on serum concentration and safety data. One patient experienced a complete response. A disease control rate, defined as stable disease or better, of 41% was observed. Conclusion: IMC-20D7S is well tolerated among patients with advanced melanoma with evidence of antitumor activity. Further investigation of this agent as monotherapy in selected patients or as part of combination regimens is warranted. ©2016 AACR. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 22 |
| Issue: | 21 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2016-11-01 |
| Start Page: | 5204 |
| End Page: | 5210 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-16-1241 |
| PROVIDER: | scopus |
| PMCID: | PMC5117650 |
| PUBMED: | 27797971 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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