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

Darovasertib with Crizotinib vs Investigator's Choice as First-Line Treatment for Patients with HLA-A2 Negative Metastatic Uveal Melanoma (OptimUM-02): A Subgroup Analysis (ESMO 2026) - No abstract available

Clinical • Metastases • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Neoadjuvant Darovasertib in Primary Uveal Melanoma: Follow-Up Data from the Phase 2 OptimUM-09 Study (ESMO 2026) - No abstract available

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

Darovasertib and Crizotinib for HLA-A*02–Positive Metastatic Uveal Melanoma: Results from the Phase 2 OptimUM-01 Study (ESMO 2026) - No abstract available

Metastases • P2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal Melanoma (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: IDEAYA Biosciences

New P3 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Darovasertib plus crizotinib vs investigator's choice as first-line treatment for patients with HLA-A2 negative metastatic uveal melanoma: Primary results from the OptimUM-02 trial. (ASCO 2026) - P2/3 | " OptimUM-02 is an open-label study of HLA-A2 negative first-line mUM patients who were randomized 2:1 to receive darova 300 mg plus crizo 200 mg BID or investigator's choice (IC) of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine). In patients with HLA-A2-negative-mUM treated in the first-line setting, darova+crizo demonstrated a clinically and significantly longer PFS, and improved ORR and DCR compared with the investigator's choice treatment. AEs were consistent with the previously reported safety profiles in each arm. These results support a potential new therapeutic standard for a disease with limited treatment options and poor prognosis."

Clinical • Late-breaking abstract • Metastases • Eye Cancer • Hepatology • Melanoma • Solid Tumor • Uveal Melanoma • HLA-A

IDEAYA Biosciences and Servier Announce First Patient Dosed in OptimUM-11 Global Phase 3 Registrational Trial of Darovasertib and Crizotinib as Adjuvant Therapy for Subjects with Uveal Melanoma (PRNewswire) - "The trial is expected to enroll approximately 450 patients who have completed primary local therapy and have an increased risk of metastasis. Patients will be eligible irrespective of HLA status and will be randomized 1:1 to receive darovasertib in combination with crizotinib for 12 months or observation."

Trial status • Uveal Melanoma

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

IDEAYA Biosciences…Provides Business Update (PRNewswire) - "Registrational OptimUM-02 trial of the darovasertib combination in metastatic uveal melanoma (mUM) met its primary endpoint; new drug application (NDA) filing is underway under the real-time oncology review program (RTOR) with completion expected in H2 2026; Updated data from Phase 2 OptimUM-01 trial (HLA*A2-positive mUM patient subset) and Phase 2 OptimUM-09 trial (neoadjuvant primary UM) to be presented at ESMO."

FDA filing • P2 data • Uveal Melanoma

Following the successful completion of a Type C meeting with the FDA earlier this year, IDEAYA and its partner, Les Laboratoires Servier (Servier), initiated a global Phase 3 registrational trial (OptimUM-11) to evaluate the darovasertib combination in the adjuvant setting of primary uveal melanoma. (PRNewswire) - "OptimUM-11 will enroll approximately 450 patients with increased risk of metastasis, irrespective of HLA status, randomized 1:1 to 12-months of treatment with the combination or observation. The primary endpoint of the trial is relapse-free survival."

Trial status • Uveal Melanoma

IDEAYA Biosciences Announces ESMO 2026 Presentations for Darovasertib and IDE849 Clinical Programs (PRNewswire) - "The presentations will feature data updates from across IDEAYA's clinical pipeline, including multiple ongoing trials of darovasertib in uveal melanoma, including the registrational Phase 2/3 OptimUM-02 trial in HLA*A2:01-negative metastatic UM (mUM), the Phase 2 OptimUM-01 trial in HLA*A2:01-positive mUM, and the Phase 2 OptimUM-09 trial in the neoadjuvant setting of primary uveal melanoma. IDEAYA's partner, Hengrui Pharma, will also present clinical trial results from their Phase 1 study of IDE849 (SHR-4849) being conducted in China in patients with small cell lung carcinoma (SCLC) and other neuroendocrine carcinomas (NECs)."

P1 data • P2 data • P2/3 data • Neuroendocrine Carcinoma • Small Cell Lung Cancer • Uveal Melanoma

IDEAYA Biosciences and Servier Provide Complete Data from Phase 2/3 Registrational OptimUM-02 Trial of the Darovasertib Combination in First Line HLA*A2:01 Negative Metastatic Uveal Melanoma in a Late-Breaking Oral Presentation at ASCO (PRNewswire) - "Darovasertib combination resulted in a statistically significant and clinically meaningful improvement in median PFS vs. investigator's choice of therapy (ICT) – 6.9 months vs. 3.1 months, HR: 0.42, 58% reduction in risk of disease progression. Significantly improved ORR (37.1% vs 5.8%) and DCR (73.3% vs. 31.1%) by BICR vs. ICT, where ~77% were treated with ipilimumab + nivolumab. OS not yet mature but early trend favoring the darovasertib combination; targeting to provide the next update as part of the pre-specified interim analysis. Manageable safety profile consistent with prior results, with a low rate of TR-SAE (9.2%) and discontinuations due to TRAEs for darovasertib (2.5%) and crizotinib (10%)."

Late-breaking abstract • P2/3 data • Uveal Melanoma

In April 2026, IDEAYA announced the U.S. Food and Drug Administration (FDA) has agreed to review their new drug application (NDA) for darovasertib in combination with crizotinib under the Oncology Center of Excellence Real-time Oncology Review (RTOR) program (PRNewswire) - "IDEAYA completed its first pre-submission in May and expects to complete the NDA filing in the second half of 2026."

FDA filing • Uveal Melanoma

Neoadjuvant darovasertib in uveal melanoma patients undergoing primary local therapy (OptimUM-10): Phase 3 trial. (ASCO 2026) - P3 | "Enrollment is ongoing, and results will determine whether OptimUM-10 may establish darovasertib prior to definitive PB as the first neoadjuvant treatment for primary UM to meaningfully reduce tumor burden and expand vision- and eye-preserving treatment options for patients. Clinical trial information: NCT07015190."

Clinical • P3 data • Diabetic Retinopathy • Eye Cancer • Melanoma • Ophthalmology • Retinal Disorders • Solid Tumor • Uveal Melanoma • GNA11 • GNAQ

IDEAYA has completed enrollment of approximately 100 HLA*A2-positive mUM patients in the single-arm Phase 2 OptimUM-01 trial of darovasertib in combination with crizotinib. (IDEAYA Biosciences Press Release) - "The company plans to present data at a major medical conference from over 85 efficacy-evaluable HLA*A2-positive mUM patients in the second half of 2026. Data will include updated ORR, PFS, and OS results, which will be used to support a potential regulatory submission to the FDA to expand the labeled use of darovasertib and/or guideline inclusion to enable the use of the darovasertib combination in HLA*A2-positive mUM patients."

Enrollment closed • P2 data • Uveal Melanoma

IDEAYA is targeting to provide a clinical data update from the ongoing Phase 2 OptimUM-09 trial at a medical conference in the second half of 2026. (IDEAYA Biosciences Press Release)

P2 data • Ocular Melanoma • Uveal Melanoma

IDEAYA is continuing site activation and patient enrollment in the Phase 3 OptimUM-10 trial of neoadjuvant darovasertib in primary uveal melanoma. (IDEAYA Biosciences Press Release) - "Full enrollment in the trial is estimated to be complete by the end of 2027, revised from prior guidance of first half of 2027."

Trial status • Uveal Melanoma

Novel uveal melanoma patient-derived cell line and organoid models show increased treatment resistance compared with commercially available cell lines. (PubMed, Melanoma Res) - "Commercial cell lines showed promising viability reduction similar to prior laboratory results with treatments, including 5-μM darovasertib, 700-nM selumetinib, 700-nM selumetinib + 1000-nM MK-2206, 500-nM sotrastaurin + 1000-nM alpelisib, and 100-nM trametinib, with overall viability reduced to 32.5% for all drugs. PDLs and PDOs may more accurately represent uveal melanoma clinical response. Demonstrating efficacy of novel therapeutics in these models could improve the likelihood of successful translation for future clinical trials, but future studies are needed to define clinically meaningful in-vitro response thresholds."

Journal • Preclinical • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1

OptimUM-10: Neoadjuvant Darovasertib in Primary Uveal Melanoma (clinicaltrials.gov) - P3 | N=520 | Recruiting | Sponsor: IDEAYA Biosciences

Trial initiation date • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

NADOM: Neoadjuvant/Adjuvant Trial of Darovasertib in Ocular Melanoma (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: St Vincent's Hospital, Sydney | Active, not recruiting ➔ Completed

Trial completion • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor

Targeting Hippo/YAP-TEAD increases the antitumor activity of darovasertib in uveal melanoma (AACR 2026) - "Darovasertib has demonstrated encouraging activity in UVM patients, and clinical trials using darovasertib as a single agent in primary UVM lesions and in combination with crizotinib in mUVM are currently ongoing. Ongoing studies are now exploring the preclinical benefit of combining darovasertib with small-molecule TEADi for the treatment of human UVM tumor xenografts in mice. Emerging evidence will be presented supporting that the Hippo YAP/TEAD pathway represents an adaptive mechanism of resistance to darovasertib treatment, and that the combination of TEADi with darovasertib may prevent the development of treatment resistance, thereby increasing the depth and duration of the anti-tumor response in UVM."

IO biomarker • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNA11 • GNAQ • LATS1 • YAP1

IDEAYA Biosciences Announces Late-Breaking Abstract Oral Presentation at ASCO 2026 to Provide Complete Data from Phase 2/3 Registrational Trial (OptimUM-02) of Darovasertib in Combination with Crizotinib in 1L HLA*A2-Negative Metastatic Uveal Melanoma (PRNewswire) - "The presentation will include detail and additional data from OptimUM-02 that were not disclosed with the company's topline release."

P2/3 data • Uveal Melanoma

IDEAYA Biosciences to Initiate New Drug Application Submission from the Darovasertib OptimUM-02 Trial under the Oncology Center of Excellence Real-time Oncology Review (RTOR) Program (IDEAYA Biosciences Press Release) - "IDEAYA plans to initiate the RTOR submission process with the first pre-submission targeted for May, with completion of the NDA filing expected in the second half of 2026."

FDA event • FDA filing • Uveal Melanoma

IDEAYA Biosciences…announced plans to issue a joint IDEAYA and Servier pre-market press release and host a conference call and webcast on Monday, April 13, 2026 at 8:00 a.m. ET to disclose topline results from their ongoing Phase 2/3 registrational trial, OptimUM-02, evaluating darovasertib in combination with crizotinib in patients with first-line HLA*A2-negative metastatic uveal melanoma (PRNewswire)

P2/3 data • Uveal Melanoma

Unveiling epigenetic mechanisms driving RasGRP3 upregulation via oncogenic Gαq signaling in uveal melanoma (AACR 2025) - "Treatment of UM cells with the Gαq inhibitor YM-254890 (YM) or the PKC inhibitor LXS-196 (LXS) for 24 hours significantly reduced all three histone modifications (H3K4me3, H3K27ac, H3K4me1) at the RasGRP3 locus. Ongoing investigations aim to delineate the precise mechanisms by which Gαq signaling drives these epigenetic changes. Our results highlight the potential of targeting specific histone modifiers as a novel therapeutic strategy for UM treatment."

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