News|Articles|April 13, 2026

First-Line Darovasertib Plus Crizotinib Yields PFS Benefit in Metastatic Uveal Melanoma

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Key Takeaways

Blinded independent review demonstrated a 58% relative reduction in progression risk with darovasertib/crizotinib vs ipilimumab/nivolumab or pembrolizumab in a randomized global setting.
Objective responses were markedly higher with the combination (37.1%) than with the control (5.8%), including complete responses exclusively in the combination arm and a median DOR of 6.8 months.
Tolerability aligned with known component toxicities; common grade 3 or higher AEs included syncope, hypertension, and diarrhea, and treatment-related serious AEs occurred at single-digit rates.
Eligibility required having systemic therapy–naive metastatic/advanced disease, RECIST 1.1 measurable disease, an ECOG performance status of 0 to 1, adequate organ function, and a 3-month or longer life expectancy.
Regulatory strategy targets accelerated approval, with an FDA submission planned for the second half of 2026 and additional detailed results expected at a 2026 medical meeting.

Frontline darovasertib plus crizotinib generated a PFS improvement vs treatment of investigator’s choice in HLA-A*02:01–negative metastatic uveal melanoma.

The first-line combination of darovasertib (IDE196) and crizotinib (Xalkori) produced a statistically significant progression-free survival (PFS) improvement vs treatment of investigator’s choice in patients with HLA-A*02:01–negative metastatic uveal melanoma, meeting the primary end point of the phase 2/3 OptimUM-02 trial (NCT05987332).¹

Top-line findings from the trial, which had a data cutoff date of January 23, 2026, showed that patients who received darovasertib plus crizotinib (n = 210) achieved a median PFS of 6.9 months by blinded independent central review (BICR) vs 3.1 months with investigator’s choice of therapy (n = 103; HR, 0.42; 95% CI, 0.30-0.59; P < .0001). Additionally, the overall response rate (ORR) was 37.1% by BICR in the darovasertib arm vs 5.8% in the control arm (P < .0001); 5 complete responses (CRs) were reported in the darovasertib arm, whereas no patients in the control arm experienced a CR. Moreover, the median duration of response (DOR) with darovasertib plus crizotinib was 6.8 months. Although the overall survival (OS) data were not mature at the time of the top-line analysis, an early OS trend favored the darovasertib arm.

“Metastatic uveal melanoma is an area of high unmet medical need with poor prognosis and short OS, and there are currently no approved therapies for [patients with] HLA-A*02:01–negative metastatic uveal melanoma,” Meredith McKean, MD, MPH, of Sarah Cannon Research Institute in Nashville, Tennessee, stated in a news release. “The data from the OptimUM-02 study provide potential practice-changing results for the [management] of first-line metastatic uveal melanoma.”

OptimUM-02 Trial Highlights

In patients with HLA-A*02:01–negative metastatic uveal melanoma, the combination of darovasertib and crizotinib significantly improved the median PFS to 6.9 months compared with 3.1 months with investigator’s choice of therapy. (HR, 0.42; 95% CI, 0.30-0.59; P < .0001).

Patients treated with the darovasertib-based combination achieved a 37.1% ORR, including 5 CRs, whereas the control arm experienced a 5.8% ORR with no CRs (P < .0001).

Plans are underway to submit a new drug application in the second half of 2026 seeking the accelerated FDA approval of darovasertib plus crizotinib in this indication.

The combination of darovasertib and crizotinib was also deemed well tolerated with a manageable safety profile that was consistent with previously reported adverse effects (AEs) and the known toxicity profiles of each individual component. The most frequently observed grade 3 or higher treatment-emergent AEs in the trial were syncope, hypertension, and diarrhea. The rate of treatment-related serious AEs among patients who received darovasertib plus crizotinib was in the single digits.

“OptimUM-02 is the first randomized study to demonstrate a statistically significant and clinically meaningful benefit in PFS in the clinical setting of first-line HLA-A*02:01–negative metastatic uveal melanoma,” Yujiro S. Hata, president and chief executive officer of IDEAYA Biosciences, added in the news release. “For patients with uveal melanoma, these results potentially offer a new treatment option that delivers a significant clinical advancement in both PFS and ORR vs currently available therapies.”

IDEAYA Biosciences plans to submit a new drug application containing these data to the FDA in the second half of 2026 to seek the accelerated approval of darovasertib plus crizotinib in this indication. Additionally, further results from OptimUM-02 are planned to be presented at a medical meeting in 2026.

What is the design of the OptimUM-02 trial?

This global study enrolled patients aged 18 or older who had received no prior systemic therapy in the metastatic or advanced setting and had measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function.²

Patients were randomly assigned to receive darovasertib plus crizotinib, or investigator’s choice of therapy with ipilimumab (Yervoy) plus nivolumab (Opdivo; n = 78) or pembrolizumab (Keytruda; n = 25).^1,2

Following the phase 2a dose-optimization portion of the trial, the phase 2 primary end point is PFS, and the phase 3 primary end point is OS.² Secondary end points include safety, ORR, DOR, quality of life, disease control rate, and time to response.

“This is a very encouraging milestone demonstrating the potential of this combination in the first-line treatment landscape for patients with metastatic uveal melanoma,” Claude Bertrand, executive vice president of research and development at Servier, concluded in the news release.¹ “Our collaboration with IDEAYA reflects a shared commitment to advancing research and bringing a potential first-in-class treatment to patients.”

References

IDEAYA Biosciences and Servier announce positive topline results from phase 2/3 registrational trial (OptimUM-02) of darovasertib in combination with crizotinib in first-line HLA-A*02:01-negative metastatic uveal melanoma. News release. IDEAYA Biosciences, Inc. April 13, 2026. Accessed April 13, 2026. https://media.ideayabio.com/2026-04-13-IDEAYA-Biosciences-and-Servier-Announce-Positive-Topline-Results-from-Phase-2-3-Registrational-Trial-OptimUM-02-of-Darovasertib-in-Combination-with-Crizotinib-in-First-line-HLA-A-02-01-Negative-Metastatic-U https://clinicaltrials.gov/study/NCT05987332 veal-Melanoma
IDE196 (darovasertib) in combination with crizotinib as first-line therapy in metastatic uveal melanoma. ClinicalTrials.gov. Updated February 17, 2026. Accessed April 13, 2026. https://clinicaltrials.gov/study/NCT05987332