Phase I clinical trial in Eastern Cooperative Oncology Group (ECOG) 0-1 patients with locally advanced or metastatic NSCLC to evaluate safety and tolerability of the compound PBF-1129, an Adenosine A2b receptor antagonist. The phase I dose escalation will be conducted 3+3 method. Pharmacokinetic (PK) data will be also obtained.

Start Date01 Oct 2018

Sponsor / Collaborator

Palobiofarma SL

[+1]

100 Clinical Results associated with PBF-1129

100 Translational Medicine associated with PBF-1129

100 Patents (Medical) associated with PBF-1129

Literatures (Medical) associated with PBF-1129

08 Nov 2023·JNCI: Journal of the National Cancer Institute

Improving combination therapies: targeting A2B-adenosine receptor to modulate metabolic tumor microenvironment and immunosuppression

Article

Author: Hoyd, Rebecca ; Uzhachenko, Roman V ; Pallerla, Aaditya ; Kikuchi, Takefumi ; Samouilov, Alexandre ; Suman, Shankar ; Amann, Joseph ; Ivanova, Alla V ; Wu, Ruohan ; Driesschaert, Benoit ; Antonucci, Anneliese ; Guan, Shuxiao ; Wei, Lai ; Zweier, Jay L ; Castro, Julio ; Tchekneva, Elena E ; Ilgisonis, Irina ; Piao, Longzhu ; Owen, Dwight H ; Ryzhov, Sergey V ; Khramtsov, Valery V ; Arasada, Rajeswara Rao ; Kanagasabai, Thanigaivelan ; Evans, Jason V ; Shanker, Anil ; Dikov, Mikhail M ; Novitskiy, Sergey V ; Park, Kyungho P ; Carbone, David P ; Goruganthu, Mounika Uttam L ; Feoktistov, Igor ; Bobko, Andrey A ; Spakowicz, Daniel J

AbstractBackgroundWe investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress in the tumor microenvironment. Novel A2B-adenosine receptor antagonist PBF-1129 was tested for antitumor activity in mice and evaluated for safety and immunologic efficacy in a phase I clinical trial of patients with non-small cell lung cancer.MethodsThe antitumor efficacy of A2B-adenosine receptor antagonists and their impact on the metabolic and immune tumor microenvironment were evaluated in lung, melanoma, colon, breast, and epidermal growth factor receptor–inducible transgenic cancer models. Employing electron paramagnetic resonance, we assessed changes in tumor microenvironment metabolic parameters, including pO2, pH, and inorganic phosphate, during tumor growth and evaluated the immunologic effects of PBF-1129, including its pharmacokinetics, safety, and toxicity, in patients with non-small cell lung cancer.ResultsLevels of metabolic stress correlated with tumor growth, metastasis, and immunosuppression. Tumor interstitial inorganic phosphate emerged as a correlative and cumulative measure of tumor microenvironment stress and immunosuppression. A2B-adenosine receptor inhibition alleviated metabolic stress, downregulated expression of adenosine-generating ectonucleotidases, increased expression of adenosine deaminase, decreased tumor growth and metastasis, increased interferon γ production, and enhanced the efficacy of antitumor therapies following combination regimens in animal models (anti–programmed cell death 1 protein vs anti–programmed cell death 1 protein plus PBF-1129 treatment hazard ratio = 11.74 [95% confidence interval = 3.35 to 41.13], n = 10, P < .001, 2-sided F test). In patients with non-small cell lung cancer, PBF-1129 was well tolerated, with no dose-limiting toxicities; demonstrated pharmacologic efficacy; modulated the adenosine generation system; and improved antitumor immunity.ConclusionsData identify A2B-adenosine receptor as a valuable therapeutic target to modify metabolic and immune tumor microenvironment to reduce immunosuppression, enhance the efficacy of immunotherapies, and support clinical application of PBF-1129 in combination therapies.

100 Deals associated with PBF-1129

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 2	-	Palobiofarma SL	-
metastatic non-small cell lung cancer	Phase 1	US	Palobiofarma SL	01 Oct 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03274479 (SITC2022) Manual	Phase 1	metastatic non-small cell lung cancer	21	PBF 1129	(ujznwfzpon) = arlkvhmryf mvlgasqxgm (dzfuqyjbrc ) View more	Positive	01 Nov 2022

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