Continuous vs intermittent adenosine 2A receptor (A2AR) inhibition in preclinical colon cancer (CC) models and in a Phase (Ph) II study of taminadenant (NIR178) + spartalizumab (PDR001) in patients (pts) with non-small cell lung cancer (NSCLC)

Lin, Chia Chi; Joerger, Markus; Grell, Peter; Chiappori, Alberto; Leal, Ticiana; Kasper, Stefan; Jérusalem, Guy; Gonçalvès, Anthony; Wolf, Juergen; Braud, Filippo de; Jonge, Maja J.A. de; Otero, Jaime; Chhagan, S.; Cipolletta, Daniela; Morris, E.; Chowdhury, Niladri Roy; Hurtado, Felipe K.; Tan, Daniel Shao-Weng

doi:10.1016/s0959-8049(20)31098-4

Cited by 5 publications

(2 citation statements)

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“… 119 Additionally, a phase 2 study of intermittent versus continuous A2AR antagonism with taminadenant plus spartalizumab in immunotherapy-naive advanced NSCLC (previously treated with one to three other therapies) showed disappointing results, with ORRs of 0%–10% across the various regimens. 120 More encouragingly, the combination of the dual A2AR/A2BR antagonist etrumadenant with carboplatin, pemetrexed, and pembrolizumab led to tumor shrinkage in all evaluable patients in a small phase 1/1b study in patients with metastatic NSCLC, including among those who had received prior immunotherapy. 121 Clinical studies continue to explore combinations of A2AR antagonists and PD-(L)1 inhibitors in NSCLC ( Table 3 ).…”

Section: Strategies For Enhancing Responses and Countering Resistance...mentioning

confidence: 99%

“…However, a subsequent phase 1b/2 study in a small cohort of patients with metastatic NSCLC with disease progression after platinum‐based chemotherapy and a prior PD‐(L)1 inhibitor suggested a lower ORR with the ciforadenant and atezolizumab combination (6.7%) than with docetaxel (21.4%) 119 . Additionally, a phase 2 study of intermittent versus continuous A2AR antagonism with taminadenant plus spartalizumab in immunotherapy‐naive advanced NSCLC (previously treated with one to three other therapies) showed disappointing results, with ORRs of 0%–10% across the various regimens 120 . More encouragingly, the combination of the dual A2AR/A2BR antagonist etrumadenant with carboplatin, pemetrexed, and pembrolizumab led to tumor shrinkage in all evaluable patients in a small phase 1/1b study in patients with metastatic NSCLC, including among those who had received prior immunotherapy 121 .…”

Section: Strategies For Enhancing Responses and Countering Resistance...mentioning

confidence: 99%

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Emerging therapeutic strategies for enhancing sensitivity and countering resistance to programmed cell death protein 1 or programmed death‐ligand 1 inhibitors in non–small cell lung cancer

Villaruz

Blumenschein

Leal

2023

Cancer

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The availability of agents targeting the programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) immune checkpoint has transformed treatment of advanced and/or metastatic non–small cell lung cancer (NSCLC). However, a substantial proportion of patients treated with these agents do not respond or experience only a brief period of clinical benefit. Even among those whose disease responds, many subsequently experience disease progression. Consequently, novel approaches are needed that enhance antitumor immunity and counter resistance to PD‐(L)1 inhibitors, thereby improving and/or prolonging responses and patient outcomes, in both PD‐(L)1 inhibitor‐sensitive and inhibitor‐resistant NSCLC. Mechanisms contributing to sensitivity and/or resistance to PD‐(L)1 inhibitors in NSCLC include upregulation of other immune checkpoints and/or the presence of an immunosuppressive tumor microenvironment, which represent potential targets for new therapies. This review explores novel therapeutic regimens under investigation for enhancing responses to PD‐(L)1 inhibitors and countering resistance, and summarizes the latest clinical evidence in NSCLC.

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Section: Strategies For Enhancing Responses and Countering Resistance...mentioning

confidence: 99%

Section: Strategies For Enhancing Responses and Countering Resistance...mentioning

confidence: 99%

Emerging therapeutic strategies for enhancing sensitivity and countering resistance to programmed cell death protein 1 or programmed death‐ligand 1 inhibitors in non–small cell lung cancer

Villaruz

Blumenschein

Leal

2023

Cancer

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GPCRs: emerging targets for novel T cell immune checkpoint therapy

Dickinson,

Yee,

Vigil

et al. 2024

Cancer Immunol Immunother

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Although immune checkpoint blockade (ICB) has become the mainstay of treatment for advanced solid organ malignancies, success in revitalizing the host anticancer immune response remains limited. G-protein coupled receptors (GPCRs) are a broad family of cell-surface proteins that have been regarded as main players in regulating the immune system, namely by mediating the activity of T lymphocytes. Among the most novel immunoregulatory GPCRs include GPR171, lysophosphatidic acid receptors (LPARs), GPR68, cannabinoid receptor 2 (CB2), and prostaglandin E receptors, many of which have shown promise in mediating antitumor response via activation of cytotoxic T cells, inhibiting immunosuppressive lymphocytes, and facilitating immune cell infiltration within the tumor microenvironment across multiple types of cancers. This paper reviews our current understanding of some of the most novel GPCRs—their expression patterns, evolving roles within the immune system and cancer, potential therapeutic applications, and perspective for future investigation. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-024-03801-7.

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