IDE397 / Ideaya Biosci - LARVOL DELTA

A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Not yet recruiting | Sponsor: IDEAYA Biosciences

Monotherapy • New P1 trial • Bladder Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Peritoneal Mesothelioma • Pleural Mesothelioma • Solid Tumor • Urothelial Cancer

IDE397 (MAT2A) (PRNewswire) - "IDEAYA has selected Dose level 2 as the go-forward dose for the IDE397 and Trodelvy clinical combination in MTAP-deleted UC and has achieved first-patient-in (FPI) in NSCLC. The next clinical update from the combination trial is planned for a medical conference in the first half of 2026."

Trial status • Non Small Cell Lung Cancer • Urothelial Cancer

IDEAYA Biosciences Announces Agenda for 10-Year Anniversary R&D Day on September 8, 2025 (PRNewswire) - "Members of IDEAYA's senior leadership team will provide an overview of the company's progress to date, including presentation of new clinical data on darovasertib in neoadjuvant uveal melanoma (UM), IDE849 (DLL3 TOP1 ADC) and IDE397 (MAT2A)..."

Clinical data • Uveal Melanoma

IDEAYA Biosciences Announces IND Submission for IDE892, a Potential Best-In-Class PRMT5 Inhibitor for MTAP-Deletion Solid Tumors (PRNewswire) - "The company is targeting to begin a Phase 1 dose escalation trial of IDE892 in MTAP-deleted lung cancer in the fourth quarter of 2025, with the goal of advancing into combination trials with IDE397...in the first half of 2026....Preclinical profile of IDE892 and mechanistic combination rationale with IDE397...inhibitor, will be presented at the 10-Year Anniversary R&D Day on September 8th."

IND • New P1 trial • Preclinical • Solid Tumor

IDEAYA Biosciences Announces Positive Data From Phase 1/2 Combination Trial of IDE397, a potential first-in-class MAT2A inhibitor, and Trodelvy in MTAP-Deletion Urothelial Cancer (PRNewswire) - "Selection of recommended Phase 2 dose is targeted by end of 2025, with next update planned for a medical conference in H1 2026....33% ORR at DL1 (3/9); 3 confirmed partial responses (cPR), including one patient with a confirmed response after the cut-off date, and 57% ORR at DL2 (3 cPR and 1 unconfirmed partial response (uPR)). The preliminary combination data is trending favorably versus historical Trodelvy monotherapy efficacy reported in metastatic UC, including 11% ORR in patients post-EV therapy (Sternschuss et al., 2025) and 23% ORR in predominantly EV-naïve patients (Powles et al., 2025)."

P1 data • Trial status • Urothelial Cancer

IDEAYA Biosciences Announces First-Patient-In for Phase 1/2 Combination Trial of IDE397, A Potential First-in-Class MAT2A Inhibitor, and Trodelvy in MTAP-Deletion Non-Small Cell Lung Cancer (PRNewswire) - "IDEAYA is conducting the trial pursuant to a clinical study collaboration and supply agreement with Gilead..."

Trial status • Non Small Cell Lung Cancer

IDEAYA Biosciences, Inc. Reports Second Quarter 2025 Financial Results and Provides Business Update (PRNewswire) - "IDEAYA will provide initial Phase 1 safety and efficacy data from two expansion cohorts in the IDE397 and Trodelvy (sacituzumab govitecan-hziy) combination trial in MTAP-deletion UC patients at the company's R&D Day September 8th, with additional data targeted for a medical conference in the first half of 2026. IDEAYA's partner, Hengrui Pharma, is conducting a multi-site, open label Phase 1 clinical trial for IDE849 in China for patients with small-cell lung cancer (SCLC). Hengrui will present clinical safety and efficacy data from over 70 patients in the trial at the International Association for the Study of Lung Cancer ('IASLC) 2025 World Conference on Lung Cancer (WCLC) taking place from September 6-9, 2025 in Barcelona, Spain. The presentation will include data from the dose escalation and multiple expansion doses. In May 2025, IDEAYA initiated a Phase 1 trial in the U.S. in SCLC. Patient dosing in NETs and other DLL3-expressing tumors is targeted by year-end 2025."

P1 data • Trial status • Neuroendocrine Tumor • Small Cell Lung Cancer • Urothelial Cancer

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

IDEAYA Biosciences, Inc. Reports First Quarter 2025 Financial Results and Provides Business Update (PRNewswire) - "IDEAYA plans to enable the wholly-owned IDE397 and IDE892 (PRMT5MTA) combination in patients with MTAP-deletion non-small cell lung cancer (NSCLC) in the second half of 2025....Initiation of evaluation of IDE849 and IDE161 combination targeted in the second half of 2025....Targeting to present preclinical combination mechanism and synergy efficacy data of IDE161 with TOP1-payload based ADCs at a medical conference in the third quarter of 2025."

New trial • Preclinical • Non Small Cell Lung Cancer

The MTA-cooperative PRMT5 inhibitor ABSK131 exhibits potent activity and broad synergistic potential in MTAP-deleted cancer models (AACR 2025) - "ABSK131 exhibits strong anti-tumor activity in MTAP-deleted lung and pancreatic cancer models and synergizes effectively with multiple therapeutic agents. These findings support the continued clinical development of ABSK131 as both a monotherapy and in combination regimens for MTAP-deleted cancers."

Late-breaking abstract • Preclinical • Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MAT2A • MTAP • PARP1

Development of SY-9453, a novel MAT2A inhibitor, for the treatment of MTAP-deficient cancers (AACR 2025) - "The encouraging clinical activity of IDE397 provides further proof-of-concept for MAT2A inhibitors in the treatment of MTAP-deficient cancers. Furthermore, SY-9453 revealed favorable PK properties and tolerability in preclinical studies. In conclusion, the current results demonstrate that SY-9453 is a novel small molecule MAT2A inhibitor with high activity in vitro and in vivo, providing a rational option for treating cancers with MTAP deficiency."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CDKN2A • MAT2A • MTAP

The allosteric MAT2A inhibitor IDE397 uniquely exploits metabolic liabilities associated with MTAP deletion to perturb DNA replication and repair (AACR 2025) - P1, P1/2 | "Observations of adaptive compensation within distinct methyltransferase pathways, such as polyamine synthesis, suggest this hierarchy is dynamic and orchestrated. The metabolic liabilities arising from MAT2A inhibition in MTAP deleted cancer cells provide a mechanistic rationale for unique therapeutic opportunities for IDE397 as a single-agent and in combination which are now being evaluated in patients (NCT04794699 and NCT05975073)."

Oncology • Solid Tumor • CDKN2A • MAT2A • MTAP

The impact of metabolite kinetics on dysregulation of essential enzymes in cancers with MTAP deficiencies (AACR 2025) - "This study provides novel insights into the metabolic vulnerabilities of MTAP-deficient cancers and the mechanisms underlying the efficacy of targeted therapies. The discovery of the metabolite exchange channel in PRMT5 and the impact of MTA/SAM ratios on inhibitor efficacy offer new avenues for drug design and combination strategies. The synergistic effect observed with concurrent MAT2A and PRMT5 inhibition presents a promising approach with the potential to profoundly alter the treatment landscape for patients with MTAP deleted cancers.Our novel findings in this study provide mechanistic support for the importance of understanding metabolite exchange in PRMT5, the crucial impact of MTA/SAM ratios on the potency of MTA-cooperative PRMT5 inhibitors, and the benefit of combination therapy with the MAT2A inhibitor IDE397."

Oncology • MAT2A • MTAP

IDEAYA Biosciences Announces Phase 1/2 Expansion for IDE397 and Trodelvy Combination in MTAP-Deletion Urothelial Cancer (PRNewswire) - "IDEAYA Biosciences...announced the initiation of a Phase 1/2 expansion in the clinical trial evaluating IDE397, its investigational, potential first-in-class, small molecule methionine adenosyltransferase 2a (MAT2A) inhibitor, in combination with Gilead's Trodelvy (sacituzumab govitecan-hziy), a Trop-2 directed antibody-drug conjugate (ADC), in methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC) based on preliminary safety and clinical efficacy data....A clinical program update on the IDE397 and Trodelvy combination is planned in 2025. In addition to the clinical trial program evaluating IDE397 in combination with Trodelvy, IDEAYA is has a monotherapy expansion study in MTAP-deletion NSCLC and UC and is expecting to initiate a wholly-owned clinical combination trial of IDE397 and IDE892, IDEAYA's potential best-in-class, MTA-cooperative PRMT5 inhibitor in the second half of 2025."

New P1/2 trial • New trial • Non Small Cell Lung Cancer • Urothelial Cancer

IDEAYA Announces Further Gilead Sciences Clinical Study Collaboration Evaluating Combination of Trodelvy and IDE397 in MTAP-Deletion NSCLC (PRNewswire) - "IDEAYA Biosciences...announced it has entered into an additional clinical study collaboration and supply agreement with Gilead Sciences, Inc...to evaluate the efficacy and safety of IDE397, its investigational, potential first-in-class, small molecule MAT2A inhibitor, in combination with Gilead's Trodelvy (sacituzumab govitecan-hziy), a Trop-2 directed antibody-drug conjugate (ADC), in methylthioadenosine phosphorylase (MTAP)-deletion non-small cell lung cancer (NSCLC)...'look forward to providing clinical program updates in 2025,'...In addition to the Phase 1/2 trial evaluating IDE397 in combination with Trodelvy in UC and NSCLC, IDEAYA is actively enrolling patients into a monotherapy expansion in MTAP-deletion NSCLC and urothelial cancer and is expecting to initiate a wholly-owned clinical combination trial of IDE397 and IDE892, IDEAYA's potential best-in-class, MTA-cooperative PRMT5 inhibitor in the second half of 2025."

Commercial • New trial • Trial status • Non Small Cell Lung Cancer • Urothelial Cancer

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

Phase 1 dose escalation (DEs) & expansion (DEx) study to evaluate the safety & efficacy of IDE397 plus sacituzumab-govitecan in patients with advanced urothelial carcinoma (UC) with MTAP deletion (MTAPdel). (ASCO-GU 2025) - P1 | "MTAPdel UC shows preferential sensitivity to TOP1 inhibitors (TOP1i) like the TROP-2 targeting-SN38 ADC sacituzumab-govitecan (SG); with less benefit from enfortumab-vedotin ([UNITE study(JCO 2023)]. DL2 is underway. Clinical trial identification: NCT 04794699"

Clinical • Metastases • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • MAT2A • MTAP • TOP1

IDEAYA Biosciences, Inc. Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (PRNewswire) - "Initiation of the Phase 3 registration-enabling trial for darovasertib in neoadjuvant UM is targeted for the first half of 2025...Targeting Phase 1/2 expansion in the first quarter of 2025 and clinical data update for IDE397 in combination with Trodelvy in MTAP-deletion UC in 2025...IDEAYA and Amgen mutually agreed to wind down the IDE397 and AMG 193 clinical combination study in February 2025, and will not pursue dose expansion...IDEAYA plans to submit a U.S. IND for the evaluation of IDE849 as a monotherapy in SCLC in the first half of 2025. Targeting to initiate the evaluation in combination with IDE161 and in NETs in the second half of 2025. Clinical data update targeted in 2025."

Clinical data • IND • New trial • Trial completion • Neuroendocrine Tumor • Small Cell Lung Cancer • Urothelial Cancer • Uveal Melanoma

IDEAYA Biosciences Announces Participation at the 43rd Annual J.P. Morgan Healthcare Conference and 2025 Corporate Guidance (PRNewswire) - "3 IND-filings targeted in 2025, representing IDEAYA's 7th, 8th, and 9th potential clinical stage precision medicine oncology program targeting solid tumors; IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor, in mid-year 2025. Combination potential with IDE397; IDE034, a potential first-in-class B7H3/PTK7 TOP1i bispecific ADC, in the second half of 2025. Combination potential with IDE161; IDE251, a potential first-in-class KAT6/7 dual inhibitor development candidate, in the second half of 2025. Combination potential with multiple programs in IDEAYA's pipeline..."

IND • 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=184 | Recruiting | Sponsor: Amgen | Trial completion date: Sep 2027 ➔ Feb 2027 | Trial primary completion date: Mar 2026 ➔ Aug 2025

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

IDE397 demonstrated deep and durable regressions in combination with PRMT5 inhibitors BMS-986504 and AMG 193 in preclinical models (PRNewswire) - "...IDEAYA had additional poster presentations at ENA 2024 highlighting preclinical data for the MAT2A and PARG programs. In the ENA 2024 concomitant publication, IDE397 demonstrated deep and durable regressions in combination with clinical stage PRMT5 inhibitors BMS-986504 and AMG 193 in multiple MTAP-deletion preclinical models."

Preclinical • Oncology • Solid Tumor

IDEAYA Biosciences, Inc. Reports Third Quarter 2024 Financial Results and Provides Business Update (PRNewswire) - "Darovasertib in 1L MUM and Neoadjuvant Uveal Melanoma (UM): Enrollment in darovasertib + crizotinib 1L HLA-A2+ MUM potential Ph2/3 registration-enabling trial is ahead of schedule and has exceeded 150 patients....Following a successful Type C meeting with the U.S. Food and Drug Administration (FDA), IDEAYA is finalizing the Phase 3 registrational trial protocol and is targeting to initiate its potential registration-enabling trial in the first half of 2025. IDE397 in MTAP-Deletion Solid Tumors: Enrollment is ongoing in the IDE397 and AMG 193 Phase 1 dose escalation, and targeting expansion in NSCLC in late 2024 to early 2025. Ongoing Phase 1 trial evaluating IDE397 in combination with Trodelvy in MTAP-deletion UC; targeting combination expansion in the fourth quarter of 2024."

Trial status • Non Small Cell Lung Cancer • Urothelial Cancer • Uveal Melanoma

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=184 | Recruiting | Sponsor: Amgen | Trial completion date: Dec 2026 ➔ Sep 2027

Combination therapy • Metastases • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

IDEAYA Announces Positive Interim Phase 1 Expansion Data of IDE397 in MTAP-Deletion Urothelial and Lung Cancer as Late-Breaker Oral Presentation at EORTC-NCI-AACR 2024 (PRNewswire) - P1 | N=180 | NCT04794699 | Sponsor: IDEAYA Biosciences | "The clinical data update in the twenty-seven (27) evaluable patients by RECIST 1.1 include: ~33% Overall Response Rate (ORR). One (1) complete response (CR) and eight (8) partial responses (PRs) by RECIST 1.1 evaluation out of twenty-seven (27) evaluable patients. Nine (9) of nine (9) responses have been confirmed by RECIST 1.1, including four (4) UC patients, of which one was a CR, three (3) squamous NSCLC patients, and two (2) adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date....Favorable adverse event (AE) profile. Approximately 18% grade 3 or higher drug-related AEs and no drug-related serious adverse events (SAEs) observed at the IDE397 30mg once-a-day expansion dose."

P1 data • Lung Adenocarcinoma • Lung Non-Small Cell Squamous Cancer • Urothelial Cancer

ENA 2024 IDE397 and Trodelvy Clinical Combination Case Study in MTAP-deletion UC (PRNewswire) - "IDEAYA reports the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC, including a PR by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation molecular responses with ctDNA reduction of greater than 95% observed that will be presented at ENA 2024. IDEAYA is targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC in Q4 2024."

Clinical data • Trial status • Urothelial Cancer