- |||||||||| onametostat (JNJ-64619178) / J&J
Trial completion date, Trial primary completion date, Metastases: A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS (clinicaltrials.gov) - Oct 11, 2023
P1, N=114, Active, not recruiting,
In summary, our data support concurrent inhibition of PRMT5 and KRAS as a promising therapeutic strategy for MTAP-deficient KRAS-mutant pancreatic cancer. Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
- |||||||||| onametostat (JNJ-64619178) / J&J
Clinical, P1 data, Journal, Metastases: Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors. (Pubmed Central) - Sep 18, 2023
Based on safety, clinical activity, PK, and PD findings, two provisional RP2Ds were selected: 1.5 mg intermittently and 1.0 mg once daily. Aside from ACC, clinical benefit was limited, and biomarkers to enrich for responsiveness to PRMT5 inhibition will be needed for further development.
- |||||||||| Combination therapeutic strategy with type I PRMT inhibition in cancer treatment (Section 20; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_8421;
We validated the synergistic effects and mechanisms of combined treatment with a type I PRMT inhibitor and a PRMT5 inhibitor (JNJ-64619178, GSK3326595/EPZ015938 or an in-house PRMT5i) using cell-based assays and in vivo studies...In vitro and in vivo studies revealed that inhibitors of type I PRMT and MAT2A (AG-270) dosing combination indeed exhibited stronger anti-cancer activity than mono-treatment...In vivo, the combination of type I PRMT inhibitor with different FLT3 inhibitors (Gilteritinib, Midostaurin, or CTS2016) led to deeper antitumor responses in a variety of FLT3-ITD AML models. Taken together, these findings support the co-administration of type I PRMT inhibitor with various therapies including epigenetic reprogramming, cancer metabolism modulation, or targeted therapies for receptor tyrosine kinases, which could benefit cancer patients as a promising therapeutic strategy.
- |||||||||| pemrametostat (GSK3326595) / Ipsen, onametostat (JNJ-64619178) / J&J
PH020-803: an MTA-cooperative and brain-penetrable PRMT5 inhibitor that selectively targets MTAP-deleted tumors (Room W224 - Convention Center) - Mar 14, 2023 - Abstract #AACR2023AACR_3161;
A pair of HCT116 isogenic cell lines (MTAP-/- and MTAP+/+) were used to determine the effects of PH020-803 on cell proliferation and intracellular symmetric dimethylarginine (SDMA) content. The present data suggest that PH020-803 is an MTA-cooperative and brain-penetrable PRMT5 inhibitor that selectively targets MTAP-deleted tumors.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, onametostat (JNJ-64619178) / J&J
Inhibition of PRMT5 Increases Sensitivity to BH3 Mimetics in Aggressive B Cell Malignancies (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_5790;
P1
The DLBCL cell lines (HBL1, TMD8, RI-1, OCI-Ly1, Karpas 422, SUDHL4, Toledo), double hit lymphoma (DHL) patient-derived xenograft (PDX) cell lines (DW19), mantle cell lymphoma (MCL) cell lines (Mino, Jeko-1), T cell acute leukemia (T-ALL) cell line (Jurkat) and Burkitt lymphoma (BL) cell line (Raji) were used to investigate the in vitro anti-cancer activity of JNJ-64619178 (Janssen Pharmaceuticals) and BH3 mimetics (venetoclax [BCL2i], S63845 [MCL-1i] and A1331852 [BCL-xLi], Selleckchem). The combination of a PRMT5 inhibitor with BH3 mimetics, especially venetoclax, is worthy of further exploration as a potential therapeutic strategy for DLBCL and MCL.
- |||||||||| onametostat (JNJ-64619178) / J&J
Journal, Epigenetic controller: Repurposing epigenetic inhibitors to target the Clostridioides difficile-specific DNA adenine methyltransferase and sporulation regulator CamA. (Pubmed Central) - Sep 20, 2022
We found that SGC0946 (an inhibitor of DOT1L), JNJ-64619178 (an inhibitor of PRMT5) and SGC8158 (an inhibitor of PRMT7) inhibit CamA enzymatic activity in vitro at low micromolar concentrations...This N-terminal arm and its modulation of exchanges between SAM (the methyl donor) and SAH (the reaction product) during catalysis of methyl transfer are, to date, unique to CamA. Our work presents a substantial first step in generating potent and selective inhibitors of CamA that would serve in the near term as chemical probes to investigate the cellular mechanism(s) of CamA in controlling spore formation and colonization, and eventually as therapeutic antivirulence agents useful in treating C. difficile infection.
- |||||||||| Review, Journal, IO biomarker: Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review. (Pubmed Central) - Aug 30, 2022
Highly significant is a durable complete response in isocitrate dehydrogenase 1-mutated glioblastoma multiforme with PRT811...Further studies are warranted, and there are clinical trials to come whose data will be telling of the efficacy of PRMT5 inhibitors in both hematologic and solid malignancies. The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials.
- |||||||||| onametostat (JNJ-64619178) / J&J
Trial completion date, Trial primary completion date, Metastases: A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS (clinicaltrials.gov) - Aug 22, 2022
P1, N=114, Active, not recruiting,
The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials. Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Jul 2022 --> Dec 2023
- |||||||||| onametostat (JNJ-64619178) / J&J
Enrollment closed, Enrollment change, Metastases: A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS (clinicaltrials.gov) - Jun 21, 2021
P1, N=113, Active, not recruiting,
Trial completion date: Jul 2022 --> Dec 2022 Recruiting --> Active, not recruiting | N=190 --> 113
- |||||||||| Adomet (S-adenosyl-L-methionine) / Abbott, GSK3326595 / GSK, JNJ-64619178 / J&J
Review, Journal: Nucleoside protein arginine methyltransferase 5 (PRMT5) inhibitors. (Pubmed Central) - Sep 13, 2020
PRMT5 selective inhibitors, GSK3326595, a substrate competitive inhibitor, and JNJ64619178, a SAM (S-adenosyl-l-methionine) mimetic/competitive inhibitor, have entered clinic trials for multiple cancer types. This review focuses on the recent developments in SAM mimetic nucleoside PRMT5 inhibitors, their SAR and structural insight based on published co-crystal structures.
- |||||||||| onametostat (JNJ-64619178) / J&J
Trial primary completion date, Metastases: A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS (clinicaltrials.gov) - May 18, 2020
P1, N=138, Recruiting,
The potency, small size, and synthetic accessibility of this compound class provide promising hit scaffold for medicinal chemists to further explore this series of PRMT5 inhibitors. Trial primary completion date: Dec 2021 --> Jul 2022
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