Tuesday, November 8, 2016

Anti-TYRP1 monclonal antibody - The next good thing for melanoma?????

I don't often publish the newest, latest and greatest.  We melanoma ratties have too often been used and abused by such things....not to mention sorely disappointed.  But....there's this...  (Check out the list of Melanoma Big Dogs as authors!)

An Open-Label, Dose-Escalation Phase I Study of Anti-TYRP1 Monoclonal Antibody IMC-20D7S for Patients with Relapsed or Refractory Melanoma.  Khalil, Postow, Ibrahim, Ludwig, Cosaert, Kambhampati, Tang, Grebennik, Kauh, Lenz, Flaherty, Hodi, Lawrence, Wolchok.  Clin Cancer Res. 2016 Oct 19. 

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.

The primary objective of this study was to 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.

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.

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.

No dose limiting toxicities?  Only constipation and fatigue?  41% disease control?  In patients with progression after at least one line of treatment????  One complete response????  

OK...so it is only in 27 patients.  It is preliminary data.  But, it has some big names behind it.  It might even work better as first line...maybe?  As we learned about anti-PD1, BEFORE ipi?  Or with other immunotherapy, as we learned with nivo AND ipi?  

Lots of questions.  Small numbers.  But, certainly something I'd be asking about if I were in need.  Hang in there ratties!!! - c 

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