1315P Phase Ib/II open-label, randomised evaluation of atezolizumab (atezo) + CPI-444 vs docetaxel as second/third-line therapy in MORPHEUS-NSCLC (non-small cell lung cancer)

Felip, Enriqueta; Lim, Farah Louise; Johnson, Melissa L.; O’Brien, Mary; Solomon, B.; Moreno, Víctor; Boni, Valentina; Swalduz, Aurélie; Goldberg, Sarah B.; Keam, Bhumsuk; Allen, Steven G.; Helms, H-J; Shemesh, Colby S.; Pintoffl, Jan; Al-Sakaff, N.; Bailey, Lorna; Sayyed, Pakeeza; Cho, B.C.

doi:10.1016/j.annonc.2020.08.1629

Cited by 7 publications

(6 citation statements)

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“…mOS has not been reported previously ( 76 ). In terms of safety, patients receiving atezolizumab and CPI-444 did not experience grade 5 adverse events or adverse events leading to drug ( 76 ). This study demonstrated that atezolizumab plus CPI-444 has a controlled safety profile and preliminary antitumor activity.…”

Section: Safety and Efficacy Of Ado-related Drugs In Lung Cancer Clin...mentioning

confidence: 57%

“…The ORR was 6.7% and 21.4%, respectively, and the mPFS was 2.3 months and 3.2 months, respectively. mOS has not been reported previously (76). In terms of safety, patients receiving atezolizumab and CPI-444 did not experience grade 5 adverse events or adverse events leading to drug (76).…”

Section: Safety and Efficacy Of Ado-related Drugs In Lung Cancer Clin...mentioning

confidence: 68%

“…The Morpheus study compared objective remission rates and safety of second-line therapy with atezolizumab plus CPI-444 and docetaxel in NSCLC patients who showed disease progression during or after treatment with platinum-based regimens and PD-L1/PD-1 checkpoint inhibitors ( 76 ). The ORR was 6.7% and 21.4%, respectively, and the mPFS was 2.3 months and 3.2 months, respectively.…”

Section: Safety and Efficacy Of Ado-related Drugs In Lung Cancer Clin...mentioning

confidence: 99%

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Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application

Wang,

Liu,

Wang

et al. 2024

Front. Immunol.

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Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.

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Section: Safety and Efficacy Of Ado-related Drugs In Lung Cancer Clin...mentioning

confidence: 57%

Section: Safety and Efficacy Of Ado-related Drugs In Lung Cancer Clin...mentioning

confidence: 68%

Section: Safety and Efficacy Of Ado-related Drugs In Lung Cancer Clin...mentioning

confidence: 99%

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Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application

Wang,

Liu,

Wang

et al. 2024

Front. Immunol.

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“…In a phase 1/1b study in NSCLC, the combination of the A2AR antagonist ciforadenant and atezolizumab was shown to have antitumor activity, including in resistant and/or refractory disease following prior PD‐(L)1 inhibitor treatment, with a disease control rate of 43% among such patients 118 . 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 .…”

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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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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“…Partial response was achieved in 9.5% patients. Ciforadenant, an A2AR antibody, has demonstrated promising results in a phase 1b/2 study (MORPHEUS) in combination with atezolizumab compared to docetaxel in later line treatment of NSCLC [41]. Median overall survival (OS) time was 11.5 months in the ciforadenant and atezolizumab combination arm, compared to 9.4 months in the control arm.…”

Section: Adenosine Pathwaymentioning

confidence: 99%

Novel immunotherapeutic drugs for the treatment of lung cancer

Peng

Wang

Stebbing

et al. 2021

Current Opinion in Oncology

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Purpose of reviewCancer cells evade immune surveillance partly due to the immunosuppressive features of the tumor microenvironment (TME). Currently approved immuno-oncology drugs for the treatment of lung cancer are aimed to inhibit immune checkpoints, such as programmed death protein-1 (PD-1), PD ligand-1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4. Despite these, researchers are currently racing to create the optimal cancer immunotherapy treatments. Recent findingsNovel immunotherapeutic drugs mainly act on activated immune cells and exert their therapeutic effects by enhancing antitumor responses. In this article, we review new therapies for the treatment of lung cancer that enhance T cell priming, remove coinhibitory signals, supply costimulatory signals and condition the TME.

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1315P Phase Ib/II open-label, randomised evaluation of atezolizumab (atezo) + CPI-444 vs docetaxel as second/third-line therapy in MORPHEUS-NSCLC (non-small cell lung cancer)

Cited by 7 publications

References 0 publications

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application

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

Novel immunotherapeutic drugs for the treatment of lung cancer

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