Evidence map›Paper›PMID 41760953›Full record

ArticleNature medicine2026

A small-molecule inverse agonist of PPARγ for advanced solid tumors: a phase 1 trial.

Matthew D Galsky, Charlene Mantia, Michaela Bowden, Joaquim Bellmunt, Benjamin Garmezy, Gopa Iyer, Daniel P Petrylak, Drew Rasco, Shilpa Gupta, Ildefonso Rodriguez-Rivera and 13 more

Registry-linked trialAbstract readClinical Trial, Phase I
In one paragraph

Article in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05929235 (A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05929235 phase1active not recruitingnot on this map

A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 (as Monotherapy or in Combination With Pembrolizumab) in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma

TypeinterventionalSponsorFlare Therapeutics Inc.Ran2023 to 2028Enrolled120ConditionsAdvanced Urothelial Carcinoma, Oral Drug Administration, Open LabelArmsFX-909, Pembrolizumab (KEYTRUDA ®), KEYTRUDA ®( Pembrolizumab)
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Matthew D GalskyMount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. matthew.galsky@mssm.edu.ORCID http://orcid.org/0000-0001-7655-9378
Charlene MantiaDana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7672-3131
Michaela BowdenFlare Therapeutics Inc., Cambridge, MA, USA.
Joaquim BellmuntDana-Farber Cancer Institute, Boston, MA, USA.
Benjamin GarmezySarah Cannon Research Institute, Nashville, TN, USA.
Gopa IyerDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5093-6099
Daniel P PetrylakSmilow Cancer Hospital, Yale New Haven Health, New Haven, CT, USA.
Drew RascoSTART Center for Cancer Research, San Antonio, TX, USA.
Shilpa GuptaCleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-8775-503X
Ildefonso Rodriguez-RiveraNEXT Oncology, San Antonio, TX, USA.
Yelena MikhailovFlare Therapeutics Inc., Cambridge, MA, USA.
Adarsh JoshiFlare Therapeutics Inc., Cambridge, MA, USA.
Phuong A NguyenFlare Therapeutics Inc., Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2393-1337
Bijal KakrechaFlare Therapeutics Inc., Cambridge, MA, USA.
Jennifer TepperFlare Therapeutics Inc., Cambridge, MA, USA.
Anne Marie CostaFlare Therapeutics Inc., Cambridge, MA, USA.
Carolyn McCroneFlare Therapeutics Inc., Cambridge, MA, USA.
Alex P RossiFlare Therapeutics Inc., Cambridge, MA, USA.
Jennifer A MertzFlare Therapeutics Inc., Cambridge, MA, USA.
Evisa GjiniFlare Therapeutics Inc., Cambridge, MA, USA.
Michael L MeyersFlare Therapeutics Inc., Cambridge, MA, USA.
Matthew I MilowskyUNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-8965-8129
Xin GaoMassachusetts General Hospital Cancer Center, Boston, MA, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of luminal lineage in urothelial carcinoma. FX-909 is a first-in-class oral small-molecule PPARγ inverse agonist. Here we report the first part of FX-909-CLINPRO-1, a phase 1A 3 + 3 dose-escalation study of FX-909, that enrolled 56 patients with advanced solid tumors, including 46 with urothelial carcinoma. The primary end point was safety and tolerability; secondary end points included recommended phase 2 dose determination, pharmacokinetics and preliminary antitumor activity. FX-909 exhibited an acceptable safety and tolerability profile. Grade ≥3 adverse events included anemia (26.8%), thrombocytopenia (21.4%), fatigue (10.7%) and hyperglycemia (7.1%). Doses of 30 mg and 50 mg daily were selected for recommended phase 2 dose optimization. Objective responses were observed in 17.5% of patients with urothelial carcinoma across all dose levels. Exploratory analyses revealed that tumor responses were enriched in patients with high PPARγ expression. FX-909 demonstrated acceptable safety and tolerability with preliminary antitumor activity, supporting further clinical development in urothelial cancer. ClinicalTrials.gov identifier: NCT05929235 .

Indexed as

Antineoplastic AgentsNeoplasmsPPAR gammaAdultAgedAged, 80 and overDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedPPAR-gamma AgonistsAntineoplastic AgentsPPAR gammaPPAR-gamma Agonists

Identifiers

PMID41760953
PMCPMC13099430

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.