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10d
A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer (clinicaltrials.gov)
P2, N=60, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended
Trial suspension
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MTAP (Methylthioadenosine Phosphorylase)
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MTAP deletion
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gemcitabine • albumin-bound paclitaxel • oxaliplatin • irinotecan • navlimetostat (BMS‐986504)
12d
Phase 1b Trial of BMS-986504 in Combination With Olaparib in Patients With MTAP Loss (clinicaltrials.gov)
P1, N=36, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jun 2026 --> Feb 2026
Enrollment open • Trial initiation date
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MTAP (Methylthioadenosine Phosphorylase)
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MTAP deletion
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Lynparza (olaparib) • navlimetostat (BMS‐986504)
20d
New P2/3 trial
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MTAP (Methylthioadenosine Phosphorylase)
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MTAP deletion
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Keytruda (pembrolizumab) • cisplatin • carboplatin • paclitaxel • albumin-bound paclitaxel • pemetrexed • navlimetostat (BMS‐986504)
20d
New P2/3 trial
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MTAP (Methylthioadenosine Phosphorylase)
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MTAP deletion
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gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS‐986504)
1m
New P1 trial
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MTAP (Methylthioadenosine Phosphorylase)
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MTAP deletion
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Lynparza (olaparib) • navlimetostat (BMS‐986504)
2ms
MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario. (PubMed, Cancer Res)
MTA-cooperative PRMT5 inhibitors such as BMS-986504/MRTX1719 and AMG 193 target the PRMT5-MTA complex, while inhibitors of the SAM synthetase methionine adenosyl transferase 2A (MAT2A), such as IDE397, deprive PRMT5 of its methyl donor SAM. In this review article, we summarize the mechanisms of action, preclinical data, and clinical data available thus far for these novel classes of oncology precision medicine and discuss potential future directions relevant to MTAP deletion as a promising synthetic lethal vulnerability for cancer therapy.
Journal
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MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
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MTAP deletion
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IDE397 • navlimetostat (BMS‐986504) • AMG 193
3ms
New P2 trial
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gemcitabine • albumin-bound paclitaxel • oxaliplatin • irinotecan • navlimetostat (BMS‐986504)
4ms
Clinical Significance of MTAP Deletions and their Overlap with Concurrent Oncogenic Driver Alterations Including EGFR in Non-Small Cell Lung Cancer. (PubMed, J Thorac Oncol)
MTAP dels frequently co-occur with oncogenic driver alterations and can develop at time of osimertinib resistance. A patient with oncogenic driver-positive, MTAP-del NSCLC had a partial response to PRMT5 inhibitor treatment. This work could inform future trials of PRMT5 and MAT2A inhibitors.
Journal
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EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
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EGFR mutation • CDKN2A deletion • MTAP deletion
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MSK-IMPACT
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Tagrisso (osimertinib) • navlimetostat (BMS‐986504)
4ms
Enrollment open
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navlimetostat (BMS‐986504)
4ms
CA240-0007: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov)
P1, N=336, Recruiting, Bristol-Myers Squibb | Trial completion date: Apr 2026 --> Dec 2027 | Trial primary completion date: Apr 2026 --> Dec 2027
Trial completion date • Trial primary completion date
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MTAP (Methylthioadenosine Phosphorylase)
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navlimetostat (BMS‐986504)
4ms
New P2 trial
|
MGMT (6-O-methylguanine-DNA methyltransferase) • MTAP (Methylthioadenosine Phosphorylase)
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navlimetostat (BMS‐986504)
6ms
Enrollment open
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gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS‐986504)