^
    5ms
    A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley) (clinicaltrials.gov)
    P2, N=256, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    Bavencio (avelumab) • Trodelvy (sacituzumab govitecan-hziy) • avipendekin pegol (NKTR-255) • dargistotug (M6223)
    1year
    First in Human Study of M6223 (clinicaltrials.gov)
    P1, N=58, Completed, EMD Serono Research & Development Institute, Inc. | Active, not recruiting --> Completed
    Trial completion
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    bintrafusp alfa (M7824) • dargistotug (M6223)
    over1year
    The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma. (PubMed, Future Oncol)
    Overall, 252 patients with advanced UC who are progression-free following first-line platinum-based chemotherapy will be randomized 1:2:2:2 to receive maintenance therapy with avelumab alone (control group) or combined with sacituzumab govitecan (anti-Trop-2/topoisomerase inhibitor conjugate), M6223 (anti-TIGIT) or NKTR-255 (recombinant human IL-15). Primary end points are progression-free survival per investigator and safety/tolerability of the combination regimens. Secondary end points include overall survival, objective response and duration of response per investigator, and pharmacokinetics.
    Review • Journal • Metastases
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    TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    Bavencio (avelumab) • Trodelvy (sacituzumab govitecan-hziy) • avipendekin pegol (NKTR-255) • dargistotug (M6223)
    2years
    Evaluation of the TIGIT+ immune subset depletion effect of the anti-TIGIT antibody M6223 (SITC 2022)
    Conclusions The results demonstrate that innate depletion of TIGIT+ immune subsets by Fc-mediated effector function plays an important role in anti-tumor immunity and suggest that immune pharmacodynamics in clinical trials should be closely monitored at early time points. Currently, M6223 is being evaluated in combination with avelumab as first-line maintenance therapy for advanced urothelial carcinoma in the phase 2 JAVELIN Bladder Medley umbrella trial ( NCT05327530 ).
    PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    Bavencio (avelumab) • dargistotug (M6223)
    2years
    Evaluation of novel anti-TIGIT antibody M6223 as a single agent and in combination with avelumab on human natural killer (NK) cell cytotoxicity (SITC 2022)
    Conclusions This study confirmed that NK cell cytotoxicity plays an important role in the anti-tumor activity of M6223 and demonstrated the additive effect of avelumab and M6223 in enhancing NK cell activation, especially in CD155+ human leukocyte antigen (HLA) class I-deficient target tumors. Currently, M6223 plus avelumab is being studied as first-line maintenance therapy for advanced UC in the phase 2 JAVELIN Bladder Medley umbrella trial ( NCT05327530 ).
    Combination therapy • PD(L)-1 Biomarker • IO biomarker
    |
    B2M (Beta-2-microglobulin) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • PVR (PVR Cell Adhesion Molecule) • NECTIN2 (Nectin Cell Adhesion Molecule 2)
    |
    Bavencio (avelumab) • dargistotug (M6223)
    over2years
    Phase I study of TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa (BA) in patients (pts) with metastatic/locally advanced solid unresectable tumours (ESMO 2022)
    9/24 and 2/17 pts receiving M6223 and M6223 + BA, respectively, achieved clinical benefit (stable disease at first on-Tx assessment); 3/24 and 2/17 patients, respectively, were on Tx for ≥20 weeks. Conclusions M6223 ± BA had an acceptable safety profile with favourable PK and target modulation effect.
    Clinical • P1 data • Combination therapy • IO biomarker
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    TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    bintrafusp alfa (M7824) • dargistotug (M6223)
    3years
    A first-in-human phase I study of M6223 (TIGIT inhibitor) as monotherapy or in combination with bintrafusp alfa in patients with metastatic or locally advanced solid unresectable tumors (SITC 2021)
    The study is currently ongoing in the United States and Canada. Trial Registration NCT04457778
    Clinical • P1 data • Combination therapy
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    PD-1 (Programmed cell death 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • TGFB1 (Transforming Growth Factor Beta 1)
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    bintrafusp alfa (M7824) • dargistotug (M6223)