darovasertib (IDE196) / Novartis, Ideaya Biosci, Servier - LARVOL DELTA

A phase 2 safety and efficacy study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma. (ASCO 2024) - P2 | "NADOM provides the first evidence that a globe-salvage neoadjuvant treatment strategy in UM is feasible, safe, and efficacious. The results suggest that PKC inhibition with darovasertib can induce clinically meaningful tumor shrinkage in patients with primary UM patients who otherwise require enucleation. Larger trials are in now progress (NCT05907954) to further quantify visual and oncological outcomes."

Clinical • P2 data • Eye Cancer • Fatigue • Hypotension • Melanoma • Ocular Melanoma • Oncology • Pruritus • Solid Tumor • Uveal Melanoma • GNA11 • GNAQ

Enucleation prevention and vision preservation in primary uveal melanoma (UM): Preliminary results from a phase II study of neoadjuvant darovasertib (ESMO 2025) - P2 | "Conclusions Darovasertib is well-tolerated & is the first Rx to show tumor shrinkage in primary UM resulting in EP, radiation dose reduction & potential for vision preservation. Based on these promising results, a registrational study is planned."

Clinical • P2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNA11 • GNAQ

Darovasertib: “OptimUM-09 primary phase 2 efficacy results in neoadjuvant uveal melanoma” ; Uveal melanoma (44th Annual J.P. Morgan Healthcare Conference, IDEAYA Biosciences)

P2 data • Oncology • Uveal Melanoma

Darovasertib: “OptimUM-09 primary phase 2 efficacy results in neoadjuvant uveal melanoma” ; Uveal melanoma (44th Annual J.P. Morgan Healthcare Conference, IDEAYA Biosciences)

P2 data • Oncology • Uveal Melanoma

2026 Corporate Objectives: Darovasertib in uveal melanoma (UM) (PRNewswire) - "(i) Topline results, including progression free survival (PFS) data, from ongoing registrational Phase 2/3 OptimUM-02 trial of the darovasertib and crizotinib combination in first line (1L) patients with HLA*A2-negative metastatic UM (mUM) are expected in Q1 '26....The topline PFS results, if positive, are anticipated to enable a potential accelerated approval filing in the United States...; (ii) Complete enrollment of approximately 80 HLA*A2-positive mUM patients in ongoing single-arm, Phase 2 OptimUM-01 trial of darovasertib in combination with crizotinib by Q2 '26; data to support a potential real world evidence (RWE) submission to the U.S. Food and Drug Administration (FDA) and/or NCCN/compendia listing in this patient subset."

Enrollment status • P2/3 data • Uveal Melanoma

Darovasertib is anticipated to be in three randomized, Phase 3 registrational trials across all stages of uveal melanoma by H1 '26 (PRNewswire) - "(i) OptimUM-02 (mUM): full enrollment of 437 patients complete; overall survival (OS) data expected to support a filing for full approval in 1L HLA*A2-negative mUM; (ii) OptimUM-10 (neoadjuvant): complete full enrollment of approximately 450 patients across enucleation and plaque brachytherapy cohorts by H1 '27; (iii) OptimUM-11 (adjuvant): initiate trial in collaboration with Servier in Q2 '26."

Enrollment status • New P3 trial • Uveal Melanoma

First reported overall survival results from a phase 1/2 study of darovasertib (OptimUM-01) plus crizotinib as first-line treatment for metastatic uveal melanoma (SMR 2025) - No abstract available

Clinical • Metastases • P1/2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

IDEAYA Biosciences Completes Targeted Full Enrollment in Randomized Pivotal Phase 2/3 Trial (OptimUM-02) of Darovasertib in Combination with Crizotinib in First-line HLA*A2-Negative Metastatic Uveal Melanoma (PRNewswire) - "IDEAYA Biosciences...has completed its targeted full enrollment of 435 patients....IDEAYA expects to report median progression-free survival (PFS) data from this trial in the first quarter 2026 to support a potential accelerated approval filing in the United States."

Enrollment closed • P2/3 data • Uveal Melanoma

Darovasertib (PRNewswire) - "Median progression-free survival (PFS) data from the Phase 2/3 trial (OptimUM-02) of darovasertib in combination with crizotinib in first line (1L) HLA*A2:01-negative mUM is on track to be reported by year-end 2025 to 1Q 2026; this data has the potential to enable an accelerated approval filing in the United States. The trial is nearing full enrollment, which remains on track to be completed by year-end."

Enrollment status • P2/3 data • Uveal Melanoma

Adjuvant therapy for primary UM (PRNewswire) - "In collaboration with Servier, IDEAYA plans to initiate a global Phase 3 combination trial of darovasertib and crizotinib as an adjuvant therapy for primary UM in the first half of 2026."

New P3 trial • Uveal Melanoma

IDEAYA Biosciences Reports Positive Median Overall Survival Data from Phase 2 Trial of the Darovasertib and Crizotinib Combination in First-line Metastatic Uveal Melanoma at the 2025 Society for Melanoma Research Congress (Nasdaq) - "Combination demonstrated median overall survival (OS) of 21.1 months, compared to reported historical mOS of approximately 12 months in published meta-analysis of metastatic uveal melanoma in the first-line setting; Median progression free survival (PFS) of 7.0 months; Confirmed overall response rate (ORR) by RECIST 1.1 of 34%, median duration of response (mDOR) of 9 months and disease control rate (DCR) of 90%"

P2 data • Uveal Melanoma

IDEAYA Biosciences Announces Positive Phase 2 Data for Darovasertib in the Neoadjuvant Setting of Primary Uveal Melanoma in a Proffered Paper Oral Presentation at ESMO 2025 (PRNewswire) - "83% (78/94) of patients demonstrated ocular tumor shrinkage, with 54% (51/94) achieving ≥20% tumor shrinkage. 57% (24/42) eye preservation rate in enucleation (EN) recommended patients, which increased to 95% (19/20) in patients achieving ≥20% ocular tumor shrinkage. 70% (26/37) of plaque brachytherapy (PB) eligible patients achieved a reduction in predicted radiation dose to the eye from baseline, resulting in 65% (24/37) of patients having lower predicted risk of vision loss 3-years post-PB treatment."

P2 data • Uveal Melanoma

IDE196-009: (Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: IDEAYA Biosciences | N=82 ➔ 160 | Trial completion date: Jan 2029 ➔ Apr 2030 | Trial primary completion date: Jan 2026 ➔ Apr 2027

Enrollment change • Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Inhibition of anti-apoptotic BCL2 overcomes adaptive resistance to co-targeting of the protein kinase FAK and MEK in GNAQ-driven uveal melanoma. (PubMed, J Biol Chem) - "Moreover, expression of a stable BCL2 mutant confers resistance to both FAKi+MEKi and FAKi+"RAF-MEK clamp" (avutometinib) treatment. Of direct translational relevance, we found that an approved BCL2 inhibitor (venetoclax) displays synergistic efficacy with FAK+MEK blockade and overcomes acquired resistance, including when combined with darovasertib, a dual PKC/PKN inhibitor limiting MEK and FAK signaling that is under clinical evaluation. Our findings suggest that resistance to FAKi+MEKi in UVM cells can be driven by an adaptive upregulation of the anti-apoptotic protein BCL2, and that, in turn, BCL2 inhibitors represent a promising precision-targeted strategy to overcome FAKi+MEKi treatment resistance and improve therapeutic outcomes."

IO biomarker • Journal • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BCL2 • GNA11 • GNAQ

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

Neoadjuvant Darovasertib in Primary Uveal Melanoma (clinicaltrials.gov) - P3 | N=520 | Recruiting | Sponsor: IDEAYA Biosciences | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Mar 2031 | Trial primary completion date: May 2027 ➔ Oct 2030

Enrollment open • Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Darovasertib: “Darovasertib is well tolerated in the neoadjuvant setting; majority of TRAEs are grade 1 & 2”; Uveal melanoma (IDEAYA Biosciences) - IDEAYA Biosciences 10-Year Anniversary R&D Day: “76% ORR (% of subjects with >20% ocular tumor shrinkage)”

P2 data • Oncology • Uveal Melanoma

IDEAYA Biosciences to Present First Median Overall Survival Data from Phase 2 Trial of the Darovasertib / Crizotinib Combination in Metastatic Uveal Melanoma at the 2025 Society for Melanoma Research Congress (PRNewswire) - "The presentation will include data from over 40 patients in the trial, including the first reported median overall survival (OS) data for the combination of darovasertib and crizotinib in mUM."

P2 data • Uveal Melanoma

Discovery of darovasertib (NVP-LXS196), a novel PKC inhibitor for the treatment of Uveal Melanoma (ACS-Fall 2025) - "The lead series was optimized for kinase and off target selectivity to afford a compound that is rapidly absorbed and well tolerated in pre-clinical species. Darovasertib is currently in clinical trials to assess efficacy in 1L HLA-A2-negative metastatic uveal melanoma patients and neoadjuvant/adjuvant setting in primary UM."

Eye Cancer • Melanoma • Solid Tumor • Uveal Melanoma • GNA11 • GNAQ

Servier and IDEAYA Biosciences Partner to Bring Darovasertib, a Promising Uveal Melanoma Treatment, to Patients Worldwide (PRNewswire) - "Under the agreement, Servier obtains the regulatory and commercial rights for darovasertib in all territories outside the United States....IDEAYA and Servier will target to launch a global Phase 3 randomized clinical trial in 2026....Under the terms of the agreement, IDEAYA will receive an upfront payment of $210 million, and be eligible for up to $100 million in regulatory approval-based milestone payments and up to $220 million in commercial milestone payments..."

Licensing / partnership • New P3 trial • Uveal Melanoma

IDEAYA Biosciences, Inc. Reports Second Quarter 2025 Financial Results and Provides Business Update (PRNewswire) - "IDEAYA is also evaluating darovasertib as a monotherapy in the neoadjuvant setting for primary UM, where the goal of treatment is to prevent enucleation (surgical eye removal), preserve vision prior to and post-plaque brachytherapy, and slow disease progression and metastasis. Initial safety and visual benefit data will be reported from the Phase 2 clinical trial from over 20 patients in the plaque brachytherapy-eligible cohort at IDEAYA's R&D Day on September 8th, followed by additional data from over 90 patients in both the enucleation-eligible and plaque brachytherapy-eligible cohorts in a Proffered Paper Oral Presentation at ESMO, taking place from October 17-21, 2025 in Berlin, Germany. Following a successful Type D meeting with the FDA in April 2025, the company initiated a randomized Phase 3 registration-enabling trial of darovasertib in the neoadjuvant setting for primary UM in the third quarter of 2025."

P2 data • Trial status • Uveal Melanoma

IDEAYA Biosciences, Inc. Reports Second Quarter 2025 Financial Results and Provides Business Update (PRNewswire) - "Median progression-free survival (PFS) data from the Phase 2/3 trial of darovasertib in combination with crizotinib in first line (1L) HLA-A2-negative MUM is on track to be reported by year-end 2025; this data has the potential to enable an accelerated approval filing in the United States. Over 350 patients have been enrolled in the trial as of August 4, 2025, and the company expects to complete full enrollment of approximately 400 patients by year-end. Based on feedback from the U.S. Food and Drug Administration (FDA), IDEAYA plans to submit median overall survival (OS) data from this trial to support full U.S. approval in HLA-A2-negative MUM. Median OS data from a single-arm, Phase 2 trial of darovasertib in combination with crizotinib will be presented at a medical conference in the fourth quarter of 2025."

P2 data • P2/3 data • Trial status • Uveal Melanoma

IDEAYA Biosciences Announces Proffered Paper Oral Presentation at ESMO 2025 for Phase 2 Clinical Trial of Neoadjuvant Darovasertib in Primary Uveal Melanoma (PRNewswire) - "IDEAYA Biosciences...announced that results from a multi-site global Phase 2 study of neoadjuvant darovasertib in primary uveal melanoma was accepted for a Proffered Paper oral presentation at the 2025 European Society of Medical Oncology (ESMO) meeting....A summary of the data from the abstract will be shared at a future date....The presentation will include data from over 90 patients in both the plaque brachytherapy and enucleation-eligible cohorts....Initiated a multi-site, global randomized Phase 3 neoadjuvant registrational trial in primary uveal melanoma (OptimUM-10) in Q3 2025."

P2 data • Trial status • Uveal Melanoma

A uveal melanoma murine model which faithfully recapitulates organotropism and dormancy (EACR 2025) - "Additionally, this model enables in vivo studies of candidate targeted drug treatments such as the PKC inhibitor darovasertib, currently in clinical trial... This model faithfully represents a unique opportunity to dissect the pathways that lead to UM hepatotropism and an extrahepatic dormancy-like phenotype as well as the opportunity of developing more effective therapeutic options in order to improve patient outcomes."

Preclinical • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

A Brief Overview of Uveal Melanoma Treatment Methods with a Focus on the Latest Advances. (PubMed, J Clin Med) - "This localized approach may provide significant benefit for patients with limited extrahepatic spread. Future research should focus on optimizing these novel strategies-tebentafusp, darovasertib, melphalan, and combination therapies-and on expanding our understanding of UM's molecular drivers to enable the development of more effective, personalized treatments."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNA11 • GNAQ