Tuesday, November 4, 2025 11/4/2025

Targeting immunosuppressive adenosine in patients with metastatic non-small cell lung cancer

Award Number: R01CA248741
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

Group Awards By:

View Award Description

Targeting immunosuppressive adenosine in patients with metastatic non-small cell lung cancer - SUMMARY/ABSTRACT Immune checkpoint inhibitors (ICIs) have transformed the management of patients with metastatic non-small cell lung cancer (NSCLC). Unfortunately, over 50% of patients do not respond to these therapies. Combination strategies with chemotherapy-ICIs show progress, but long-term responses remain rare, pointing to the role for other tumor-associated mechanisms affecting functionality of immune cells. Adenosinergic signaling has recently emerged as a powerful immuno-metabolic regulator within the tumor microenvironment (TME) exploited by tumors to promote their growth and suppress immunity. Preclinical studies on interference with adenosine generation or signaling through A2A and A2B adenosine receptors (A2BAR) have demonstrated efficacy in relieving this immunosuppression by reducing stress in the TME and decreasing expression of key adenosine-generating enzymes, thereby enhancing efficacy of immune checkpoint inhibition. A2BAR blockade in particular enhanced anti-tumor immunity through both a reduction in myeloid-derived suppressor cell differentiation and an enhancement of the capacity of dendritic cells to evoke anti-tumor T cell responses. These findings provide strong rationale for clinical applications of A2BAR antagonists in combination with current ICIs. To determine whether disruption of A2BAR signaling has the potential to improve upon single agent PD-1 immunotherapy, we propose a phase Ib clinical trial testing the A2BAR antagonist PBF-1129 in combination with nivolumab in patients with metastatic NSCLC. The primary objective of the clinical study is to evaluate the safety and tolerability of combination PBF-1129 with nivolumab; preliminary evidence of efficacy will be evaluated in an expansion cohort. Analysis of pre- and on- treatment blood and tumor samples will be conducted to evaluate the correlation between and immunological parameters and adenosine generation and signaling, and to evaluate the efficacy of PBF-1129 in targeting adenosine-mediated immunosuppression. Finally, we intend to further elucidate mechanisms of metabolic TME and immune regulation by adenosine in pre-clinical cancer models and test the combined PBF-1129/anti-PD-1 approach to ameliorate metabolic TME using a novel imaging modality. Together, we expect that A2BAR antagonist treatment combined with nivolumab will be a safe, effective approach targeting different mechanisms of immunosuppression and tumor growth in metastatic NSCLC patients, that we will uncover immunological profiles reflective of adenosinergic signaling disruption in these patients, and that we will demonstrate the utility of a novel combined imaging approach for evaluation of adenosine targeting in the TME.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $741,840 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	001	5	5/29/2025	NON-COMPETING CONTINUATION	$74,183
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	5	2/17/2025	NON-COMPETING CONTINUATION	$667,657
														Subtotal = $741,840

Issue Date FY: 2024 ( Subtotal = $704,749 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	4	3/25/2024	NON-COMPETING CONTINUATION	$667,657
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	001	4	4/24/2024	NON-COMPETING CONTINUATION	$37,092
														Subtotal = $704,749

Issue Date FY: 2023 ( Subtotal = $380,473 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	3	7/10/2023	NON-COMPETING CONTINUATION	$380,473
														Subtotal = $380,473

Issue Date FY: 2022 ( Subtotal = $559,834 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	2	3/16/2022	NON-COMPETING CONTINUATION	$514,130
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	001	2	4/25/2022	NON-COMPETING CONTINUATION	$45,704
														Subtotal = $559,834

Issue Date FY: 2021 ( Subtotal = $577,069 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	000	1	2/12/2021	NEW	$577,069
														Subtotal = $577,069

Grand Total All Awards = $2,963,965

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting immunosuppressive adenosine in patients with metastatic non-small cell lung cancer

Award Number: R01CA248741

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer