AMG 193 / Amgen - LARVOL DELTA

A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov) - P1/2 | N=329 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=649 ➔ 329

Enrollment change • Enrollment closed • Brain Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CDKN2A • MTAP

Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor (MAT2Ai) in MTAP deleted(del) non-small cell lung cancer (NSCLC) and urothelial cancer (UC) (EORTC-NCI-AACR 2024) - P1, P1/2 | "IDE397 provides preliminary clinical proof of concept for MAT2A inhibition in MTAPdel tumors with manageable safety & antitumor activity in pre-treated NSCLC & UC. Expansion of IDE397 monotherapy is ongoing, as well as in combination with sacituzumab-govitecan (Trodelvy®) (NCT04794699), and AMG 193 (NCT05975073)."

Late-breaking abstract • P1 data • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • MAT2A • MTAP

AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients With MTAP-Deleted Cancers. (PubMed, Cancer Discov) - "AMG 193 synergizes with chemotherapies or the KRAS G12C inhibitor sotorasib in vitro, and combination treatment in vivo significantly inhibits tumor growth. AMG 193 is demonstrating promising clinical activity, including confirmed partial responses in patients with MTAP-deleted solid tumors from an ongoing phase 1/2 study."

Journal • Preclinical • Oncology • Solid Tumor • KRAS • MTAP

First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase 1 dose exploration. (PubMed, Ann Oncol) - "AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP-deleted solid tumors was observed based on ORR and ctDNA clearance."

Journal • P1 data • Biliary Cancer • Biliary Tract Cancer • Fatigue • Gastrointestinal Cancer • Hepatology • Immunology • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CDKN2A • MTAP

Phase I dose escalation and initial dose expansion results of AMG 193: A MTA-cooperative PRMT5 inhibitor, in patients (pts) with MTAP-deleted solid tumors (ESMO 2024) - P1/2 | "AMG 193 demonstrated a favorable safety profile, no evidence of clinically significant myelosuppression as observed with first generation PRMT5 inhibitors, and encouraging antitumor activity in solid tumors, including NSCLC, PDAC and BTC. Table: 604O Antitumor activity CI, confidence interval; CR, complete response; DCR, disease control rate; NE, not estimable; ORR, objective response rate; PD, progressive disease; c/u PR, confirmed/unconfirmed partial response; QD, once daily; SD, stable disease."

Clinical • P1 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MTAP

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 • Hematological Disorders • Oncology • MAT2A • MTAP

A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov) - P1/2 | N=649 | Recruiting | Sponsor: Amgen | Trial completion date: Nov 2028 ➔ Jun 2028 | Trial primary completion date: Dec 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Brain Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CDKN2A • MTAP

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (SNO 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (WFNOS 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MTAP

A Phase 2 Study of AMG 193 in Participants With MTAP-deleted Advanced NSCLC (MTAPESTRY 201) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Amgen | Trial completion date: Sep 2029 ➔ Nov 2030 | Trial primary completion date: Sep 2027 ➔ Nov 2028

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Manufacture of a key intermediate in the synthesis of AMG 193 using continuous manufacturing and biocatalysis (ACS-Fall 2025) - "The salt form offers a significant purity upgrade and favorable physical properties compared with CFAM freebase, which was targeted in early phase deliveries. To date, >900 kg of CFAM.HCl has been produced in high quality (100 A% purity, meeting all proposed commercial specifications) to support fast-moving clinical supply demands."

MTAP

Development of an Early-Phase Process for Manufacture of AMG 193 (ACS-Fall 2025) - "This presentation summarizes the route selection, process optimization and execution of this first process on scale to supply metric kilogram quantities of the drug substance in a multi-batch campaign. Additionally, further process optimization is described which featured improvements in efficiency and plant-fit, as well as enhanced impurity-control to support the target commercial control strategy."

MTAP

A Study Evaluating AMG 193 in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103) (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: Amgen | N=188 ➔ 350

Enrollment change • Oncology • Pancreatic Cancer • Solid Tumor

A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov) - P1/2 | N=53 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Aug 2025 ➔ Jan 2026 | Trial primary completion date: Aug 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

TARGETING ARGININE METHYLTRANSFERASE PRMT5 AS A PROMISING THERAPEUTIC STRATEGY IN NKTCL (ICML 2025) - "Druggability was evaluated in NKTCL cell lines and mouse models using PRMT5 inhibitors GSK3326595 and AMG193. Overall, this study is the first to demonstrate PRMT5 overexpression in NKTCL and its vulnerability to targeted therapy. Both monotherapy with PRMT5 inhibitors and combination treatments show significant antitumor effects, providing new insights for the further treatment of this disease."

IO biomarker • Lymphoma • Natural Killer/T-cell Lymphoma • CD4 • CDKN2A • MTAP • PRMT5

TARGETING ARGININE METHYLTRANSFERASE PRMT5 AS A PROMISING THERAPEUTIC STRATEGY IN NKTCL (EHA 2025) - "Druggability was evaluated in NKTCL cell lines and mouse models using PRMT5 inhibitors GSK3326595 and AMG193. Overall, this study is the first to demonstrate PRMT5 overexpression in NKTCL and its vulnerability to targeted therapy. Both monotherapy with PRMT5 inhibitors and combination treatments show significant antitumor effects, providing new insights for the further treatment of this disease."

IO biomarker • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD4 • CDKN2A • MTAP • PRMT5

A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov) - P1/2 | N=649 | Recruiting | Sponsor: Amgen | Trial completion date: Jun 2028 ➔ Nov 2028 | Trial primary completion date: Aug 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Brain Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CDKN2A • MTAP

OncoKBTM, MSK's precision oncology knowledge base: 2024 updates (AACR 2025) - "OncoKB promoted BRAF fusions to Level 1 following inclusion as patient eligibility criteria in the FDA drug label for tovorafenib (low-grade glioma). Additionally, OncoKB included KRAS G12C in colorectal cancer and IDH1 mutations in myelodysplastic syndromes as Level 1 following FDA approval of adagrasib + cetuximab and ivosidenib, respectively...Lastly, novel biomarkers including FBXW7 and PPP2R1A alterations (endometrial and ovarian cancer), SMARCA4 mutations (non-small cell lung cancer and esophageal adenocarcinoma) and MTAP deletions (all solid tumors) were included in OncoKB based on compelling preclinical and emerging clinical evidence in association with lunresertib + camonsertib, PRT3789, and AMG193 and MRTX1719, respectively...OncoKB also implemented major software updates to support data integration into the EPIC platform. Future OncoKB efforts are focused on whole genome/exome curation, inclusion of biomarkers for non-NGS-based precision oncology therapies,..."

Tumor mutational burden • Brain Cancer • CNS Tumor • Colorectal Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Glioma • Hematological Malignancies • Lung Cancer • Microsatellite Instability • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Intestinal Carcinoma • Solid Tumor • BRAF • FBXW7 • IDH1 • KRAS • MSI • MTAP • POLD1 • PPP2R1A • SMARCA4 • TMB

Targeting RNA splicing sensitizes MTAP-deleted cancers to MTA-cooperative PRMT5 inhibitors (AACR 2025) - "AMG 193, currently in Phase 1/2 trials, is an MTA-cooperative PRMT5 inhibitor that is showing promise as a targeted therapy in MTAP-deleted tumors...Additional resistance and sensitization pathways identified from the CRISPR screens are currently being evaluated using in vitro and in vivo assays. Furthermore, clinical biomarker datasets from the ongoing early phase trials will be utilized to validate these preclinical findings."

Oncology • MTAP

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors with MTAP loss (AACR 2025) - "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 are clinical-stage MTA-cooperative PRMT5 inhibitors for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant. Oral administration of TNG456 drives dose-dependent antitumor activity including durable tumor regressions and complete responses in multiple cell line- and patient-derived xenograft models. With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including gliomas and CNS metastases."

Brain Cancer • CNS Tumor • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

A Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 Alone or in Combination With Other Therapies in Subjects With Homozygous MTAP-Deletion Advanced Thoracic Tumors (Master Protocol) (ChiCTR) - P=N/A | N=312 | Not yet recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • MTAP • PD-L1

Discovery of AMG 193, an MTA-Cooperative PRMT5 Inhibitor for the Treatment of MTAP-Deleted Cancers. (PubMed, J Med Chem) - "Preclinical data indicate that AMG 193 is brain-penetrant. AMG 193 is currently in Phase I/II clinical trials for the treatment of advanced MTAP-deleted solid tumors."

Journal • Oncology • Solid Tumor • CDKN2A • MTAP

A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov) - P1/2 | N=53 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=184 ➔ 53 | Trial completion date: Feb 2027 ➔ Aug 2025

Enrollment change • Enrollment closed • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

A Phase 2 Study of AMG 193 in Participants With MTAP-deleted Advanced NSCLC (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Amgen | Trial completion date: Feb 2029 ➔ Sep 2029 | Trial primary completion date: Feb 2027 ➔ Sep 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of AMG 193 in Subjects With Advanced MTAP-null Solid Tumors (clinicaltrials.gov) - P1/2 | N=649 | Recruiting | Sponsor: Amgen | Trial completion date: Jan 2028 ➔ Jun 2028

Trial completion date • Brain Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CDKN2A • MTAP