ArticleNature communications2025
MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03435250 (A Phase 1 Study of AG-270 in the Treatment of Subjects With Advanced Solid Tumors or Lymphoma With Homozygous Deletion of MTAP), which is not on this map. Cited by 35 papers, 2 of them syntheses that pooled 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.
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.
A Phase 1 Study of AG-270 in the Treatment of Subjects With Advanced Solid Tumors or Lymphoma With Homozygous Deletion of MTAP
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Genomics of Primary and Metastatic Cutaneous Melanoma: A Systematic Review and Meta-Analysis.American journal of clinical dermatology · 2026Pooled it
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- An Accessible Approach to Molecular and Biomarker Testing for Risk Stratification in Oral Cavity Squamous Cell Carcinoma.Head and neck pathology · 2026Article
- Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer cells.iScience · 2026Article
- A functional missense variant iniScience · 2026Article
- Review
- TNG961 Is a Selective Oral HBS1L Molecular Glue Degrader for the Treatment of FOCAD-Deleted Cancers.Cancer discovery · 2026Article
- MTAP Deficiency as a Metabolic Vulnerability in Cancer: Implications for Synthetic Lethal Therapy.Cancer science · 2026Review
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Methionine restriction and mimetics to ameliorate human aging and disease.Trends in endocrinology and metabolism: TEM · 2026Review
- Inactivation of PRMT5 by PARP Inhibitors Confers High Susceptibility in MTAP-Deficient Cancers.Cancers · 2026Article
- Therapeutic vulnerabilities exposed by the 9p21 loss identified through multiparametric drug screening inform rational combination strategies.NPJ precision oncology · 2026Article
- Review
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario.Cancer research · 2026Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Recent Advances in Targeted Therapies for Adult Gliomas.Current neurology and neuroscience reports · 2026Review
- The actionable transcriptome: a framework for incorporating RNA sequencing into precision oncology.Nature reviews. Clinical oncology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.gov Identifier: NCT03435250). Eligible patients had tumors with homozygous deletion of CDKN2A/MTAP and/or loss of MTAP protein by immunohistochemistry. Patients received AG-270/S095033 once daily (QD) or twice daily (BID) in 28-day cycles. The primary objective was to assess the maximum tolerated dose (MTD) of AG-270/S095033. Secondary objectives included safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Forty patients were treated with AG-270/S095033. Plasma concentrations of AG-270/S095033 increased with dose. Maximal reductions in plasma SAM concentrations ranged from 54% to 70%. Analysis of paired tumor biopsies showed decreases in levels of symmetrically di-methylated arginine (SDMA) residues. Reversible increases in liver function tests, thrombocytopenia, anemia and fatigue were common treatment-related toxicities. Two partial responses were observed; five additional patients achieved radiographically confirmed stable disease for ≥16 weeks. AG-270/S095033 has a manageable safety profile. Our data provide preliminary evidence of clinical activity and proof-of-mechanism for MAT2A inhibition.
Indexed as
Identifiers
What OpenQuestion holds
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.