July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Safety, efficacy and biology of the gp100 TCR-based bispecific T cell redirector IMCgp100 in advanced uveal melanoma
Author Affiliations & Notes
  • Richard D. Carvajal
    Medicine, Columbia University Medical Center, New York, New York, United States
  • Joseph Sacco
    Clatterbridge Cancer Center, Liverpool, United Kingdom
  • Paul Nathan
    Mount Vernon, Mt Vernon, United Kingdom
  • Marlana Orloff
    Thomas Jefferson Medical Center, Philadelphia, Pennsylvania, United States
  • Nicola Little
    Aptus Research, London, United Kingdom
  • Cheryl McAlpine
    Immunocore, Ltd, Oxford, United Arab Emirates
  • David Krige
    Immunocore, Ltd, Oxford, United Arab Emirates
  • Namir Hassan
    Immunocore, Ltd, Oxford, United Arab Emirates
  • Ann-Marie Hulstine
    Immunocore, Ltd, Oxford, United Arab Emirates
  • Christina Coughlin
    Immunocore, Ltd, Oxford, United Arab Emirates
  • Takami Sato
    Thomas Jefferson Medical Center, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Richard Carvajal, None; Joseph Sacco, None; Paul Nathan, Immunocore (F); Marlana Orloff, None; Nicola Little, Immunocore (F); Cheryl McAlpine, Immunocore (E); David Krige, Immunocore (E); Namir Hassan, Immunocore (E); Ann-Marie Hulstine, Immunocore (E); Christina Coughlin, Immunocore (E); Takami Sato, Immunocore (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3622. doi:
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      Richard D. Carvajal, Joseph Sacco, Paul Nathan, Marlana Orloff, Nicola Little, Cheryl McAlpine, David Krige, Namir Hassan, Ann-Marie Hulstine, Christina Coughlin, Takami Sato; Safety, efficacy and biology of the gp100 TCR-based bispecific T cell redirector IMCgp100 in advanced uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3622.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Uveal melanoma (UM) is characterized by low PD-L1 expression, low mutational burden and limited efficacy with checkpoint inhibition. IMCgp100 is a bispecific T cell redirector with an affinity-enhanced TCR recognizing gp100 and an anti-CD3 scFV. Two phase 1 trials evaluated safety, pharmacokinetics, pharmacodynamics and efficacy for IMCgp100 administered IV weekly in HLA-A2+ patients (pts): (1) a first in human study enrolling pts with melanoma including a cohort with advanced UM (n=16) where the intra-patient escalation (IE) dosing regimen was defined and (2) a second study with dose escalation of the IE regimen for pts with advanced UM 9N=19) in vestigating increasing exposures with the altered regimen, and is reported here.

Methods : Endpoints included overall response rate (ORR) by RECISTv1.1, progression free survival (PFS), and overall survival (OS). THe IE phase 1 trial allowed treatment beyond progression assessed by modified immune-related response criteria in specific settings. The IE regimen was designed to mitigate toxicity with reduced doses of 20 mcg and 30 mcg administered at weeks 1 and 2 and dose escalation implemented at dose 3 (day 15).

Results : The most frequent adverse events (AE, any grade) were rash (90%), pruritus (90%) and edema (63%). The most frequent grade 3 or 4 AE was hypotension (16%). The RP2D was 68 mcg defined with DLT of transaminase elevations. The ORR was 11% (2/19 evaluable) with an additional 5 patients achieving minor (-10 to -29% reduction) responses (26%) including pts treated with prior checkpoint inhibiton and elevated LDH. Median PFS by RECISTv1.1 was 5.6 months and the 1 year PFS rate by irRC was 62%. The 1 year OS rate in the IE trial was 73% (95% CI [46, 88]) and median OS has not been reached with median follow up of 12.8 months. With 3 doses of IMCgp100, immunofluorescence studies demonstrate an influx of PD-1+/CD8+ T cells in the tumor bed associated with strong PD-L1 expression. Further, increased T cells are observed in the setting of resistance and tumor progression.

Conclusions : These studies demonstrate preliminary safety and immune biology as well as promising efficacy in advanced UM. The pivotal trials evaluating the IE regimen in advanced UM are enrolling (NCT03070392; NCT02570308).

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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