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    DRUG:

    utomilumab (PF-05082566)

    i
    Other names: PF-05082566 , PF-2566, PF-5082566, PF05082566, PF2566, PF5082566, PF 05082566, PF 2566, PF 5082566
    Company:
    Novartis, Pfizer
    Drug class:
    CD137 agonist
    Related drugs:
    29d
    Tumor microenvironment changes after treatment with avelumab and immune- stimulating agent combinations in patients with advanced solid tumors. (PubMed, Res Sq)
    Methods We performed whole exome sequencing (WES), bulk RNAseq, multiplex immunofluorescence (mIF) and chromogenic immunohistochemistry (IHC) on tumor tissue and flow cytometry of the peripheral blood to study longitudinal changes following the combination of avelumab with utomilumab (a 4-1BB agonist) (arm A), PF-04518600 (an OX40 agonist) (arm B), utomilumab and PF-04518600 (arm C) and utomilumab and radiotherapy (arm D) in phase I/II study (NCT03217747). Conclusions Our findings, though limited, highlight genomic differences between histologic subsets and outcome as well as the need for combination strategies that drive the recruitment and/or priming of anti-tumor T cells and address low immune permissive tumor states in patients with advanced solid tumors. Clinical trial registration: This clinical trial was registered on clinicaltrials.gov NCT03217747.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CCNE1 (Cyclin E1) • IFNG (Interferon, gamma) • TTN (Titin)
    |
    TP53 mutation • KRAS mutation • KRAS G12C • KRAS G12D • TMB-L • KRAS G12
    |
    Bavencio (avelumab) • utomilumab (PF-05082566) • ivuxolimab (PF-04518600)
    2ms
    Utomilumab, Cetuximab, and Irinotecan Hydrochloride in Treating Patients With Metastatic Colorectal Cancer (clinicaltrials.gov)
    P1, N=34, Completed, M.D. Anderson Cancer Center | Trial completion date: Dec 2026 --> Dec 2025 | Trial primary completion date: Dec 2026 --> Dec 2025 | Active, not recruiting --> Completed
    Trial completion • Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability)
    |
    MSI-H/dMMR • RAS mutation
    |
    Erbitux (cetuximab) • irinotecan • utomilumab (PF-05082566)
    3ms
    Development of a nanoparticle-based immunotherapy targeting CD137 for nasopharyngeal carcinoma treatment. (PubMed, Theranostics)
    Urelumab and utomilumab, are two agonistic anti-CD137 antibodies that are most advanced in clinical trials but suffer from liver toxicity and low potency, respectively. In contrast to ure-MSNs, rhCD137-MSN treatment did not induce liver damage, thereby demonstrating a more favorable safety profile than ure-MSNs. This study identifies a formulation of rhCD137L on MSNs that combines high potency with excellent safety.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • TNFRSF9 (TNF Receptor Superfamily Member 9)
    |
    utomilumab (PF-05082566) • urelumab (BMS-663513)
    4ms
    NCI-2018-01118: Avelumab, Utomilumab, Anti-OX40 Antibody PF-04518600, and Radiation Therapy in Treating Patients With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=173, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2025 --> Apr 2026
    Trial completion date
    |
    Bavencio (avelumab) • utomilumab (PF-05082566) • ivuxolimab (PF-04518600)
    8ms
    The AVIATOR Study: Trastuzumab and Vinorelbine With Avelumab OR Avelumab & Utomilumab in Advanced HER2+ Breast Cancer (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Adrienne G. Waks | Trial completion date: May 2025 --> May 2026
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    HER-2 positive • HER-2 amplification
    |
    Herceptin (trastuzumab) • Perjeta (pertuzumab) • Bavencio (avelumab) • vinorelbine tartrate • utomilumab (PF-05082566)
    10ms
    InCITe: Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Stage IV or Unresectable, Recurrent Triple Negative Breast Cancer (clinicaltrials.gov)
    P2, N=150, Recruiting, Laura Huppert, MD, BA | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026
    Trial completion date • Trial primary completion date • Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 negative
    |
    Bavencio (avelumab) • Mektovi (binimetinib) • pegylated liposomal doxorubicin • Trodelvy (sacituzumab govitecan-hziy) • utomilumab (PF-05082566) • ivuxolimab (PF-04518600)
    12ms
    Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma (clinicaltrials.gov)
    P1, N=16, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jun 2024 | Trial primary completion date: Dec 2024 --> Jun 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1)
    |
    CD20 positive
    |
    carboplatin • Imbruvica (ibrutinib) • Rituxan (rituximab) • Bavencio (avelumab) • cyclophosphamide • ifosfamide • etoposide IV • Truxima (rituximab-abbs) • utomilumab (PF-05082566)
    1year
    Rituximab + Immunotherapy in Follicular Lymphoma (clinicaltrials.gov)
    P1, N=24, Terminated, Dana-Farber Cancer Institute | Phase classification: P1b --> P1 | Active, not recruiting --> Terminated; Stopped was stopped prematurely due to drug manufacturer withdrawing supply/funding. Patients already enrolled on study were allowed to continue treatment.
    Phase classification • Trial termination
    |
    Rituxan (rituximab) • Bavencio (avelumab) • utomilumab (PF-05082566) • ivuxolimab (PF-04518600)
    over1year
    NCI-2018-01118: Avelumab, Utomilumab, Anti-OX40 Antibody PF-04518600, and Radiation Therapy in Treating Patients with Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=173, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD8 (cluster of differentiation 8)
    |
    Bavencio (avelumab) • utomilumab (PF-05082566) • ivuxolimab (PF-04518600)
    over1year
    A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley) (clinicaltrials.gov)
    P1/2, N=409, Terminated, Pfizer | Phase classification: P1b/2 --> P1/2
    Phase classification • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    Bavencio (avelumab) • vidutolimod (CMP-001) • utomilumab (PF-05082566) • PD 360324 • ivuxolimab (PF-04518600)
    over1year
    ZUMA-11: Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Adults With Refractory Large B-cell Lymphoma (clinicaltrials.gov)
    P1, N=15, Terminated, Kite, A Gilead Company | Phase classification: P1/2 --> P1
    Phase classification • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    cyclophosphamide • Yescarta (axicabtagene ciloleucel) • fludarabine IV • utomilumab (PF-05082566)
    almost2years
    Utomilumab, Cetuximab, and Irinotecan Hydrochloride in Treating Patients With Metastatic Colorectal Cancer (clinicaltrials.gov)
    P1, N=42, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    MSI (Microsatellite instability)
    |
    MSI-H/dMMR • RAS mutation
    |
    Erbitux (cetuximab) • irinotecan • utomilumab (PF-05082566)