Pharmacodynamic (PD) changes in tumors and peripheral blood T cell receptor (TCR) repertoire in a phase I study combining OX40 (PF-04518600) and 4-1BB (utomilumab) agonistic monoclonal antibodies (mAbs)

Hamid, Omid; Hu‐Lieskovan, Siwen; Ros, Willeke; Diab, Adi; El-Khoueiry, Anthony B.; Thompson, John A.; Eskens, F.; Jp, Spano; Angevin, Eric; Rizvi, Naiyer A.; Wasser, Jeffrey S.; Ott, Patrick A.; Chiappori, Alberto; Joh, Tenshang; Krupka, Heike I.; Potluri, Shobha; Wang, X.; Ganguli, Bishu J.; Chou, Jeffrey; Doi, Toshihiko

doi:10.1093/annonc/mdy288.057

Cited by 2 publications

(1 citation statement)

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“…In the same population, another ongoing phase 1 trial of GSK3174998 administered as monotherapy or combined with pembrolizumab (anti-PD-1 Ab) showed no dose-limiting toxicities 57. The combination of agonistic mAb against OX40 (PF-8600) and 4-1BB (utomilumab) increased the expression of markers and genes related to immune activation in paired biopsies after 6 weeks of treatment when compared with baseline 58. Data about efficacy are not yet published.…”

Section: Targeting Ox40 In Clinical Trialsmentioning

confidence: 99%

New pathways in immune stimulation: targeting OX40

et al. 2020

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Immune checkpoint blockers (ICB) reinvigorate the immune system by removing the molecular brakes responsible for the scarce activity of immune phenotypes against malignant cells. After having proven their remarkable role as monotherapy, combinations of anti-Programmed cell death 1 (PD-1)/Programmed death-ligand 1 (PD-L1) agents with cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibodies, chemotherapy and/or anti-angiogenic compounds provide unprecedented results and durable responses across a variety of tumour types. Nevertheless, the main drawbacks of ICB are represented by primary and acquired resistance, translating into disease progression, as well as by immune-related toxicities. In this sense, novel strategies to foster the immune system through its direct stimulation are being tested in order to provide additional clinical improvements in patients with cancer. In this scenario, the co-stimulatory molecule OX40 (CD134) belongs to the next generation of immune therapeutic targets. Preliminary results of early clinical trials evaluating OX40 stimulation by means of different agents are encouraging. Here we review the rationale of OX40 targeting, highlighting the combination of OX40-directed therapies with different anticancer agents as a potential strategy to foster the immune system against malignant phenotypes.

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Section: Targeting Ox40 In Clinical Trialsmentioning

confidence: 99%