IDEAYA Announces First-Patient-In for Company-Sponsored Phase 2 Clinical Trial Evaluating Darovasertib in (Neo)Adjuvant Uveal Melanoma

• Dosed a first patient in a company-sponsored global Phase 2 clinical trial evaluating darovasertib as neoadjuvant and adjuvant therapy in primary uveal melanoma (UM)
• Preliminary clinical activity observed in primary UM, including tumor shrinkage in 9 of 9 patients following neoadjuvant therapy with darovasertib as monotherapy or in combination with crizotinib, two of whom were spared enucleation and preserved vision
• Targeting clinical data update in the fourth quarter of 2023 from the ongoing NADOM IST evaluating single-agent darovasertib as neoadjuvant therapy in primary UM patients
• ­(Neo)adjuvant UM has no approved systemic therapies with an annual incidence of ~8,700 patients and estimated prevalence of ~100,000 patients aggregate in the U.S. and Europe

SOUTH SAN FRANCISCO, Calif., Aug. 16, 2023 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced the achievement of First-Patient-In for the company-sponsored Phase 2 clinical trial evaluating darovasertib as neoadjuvant and adjuvant therapy in primary uveal melanoma (UM) patients. 

"We are excited to dose our first patient in this Phase 2 clinical trial. Our recently reported preliminary clinical data in the neoadjuvant setting showed compelling evidence of anti-tumor activity – with observed tumor shrinkage in 9 patients, including two patients who were able to avoid enucleation. These data support further clinical evaluation of darovasertib to determine its potential as a neoadjuvant and adjuvant therapy," said Dr. Darrin Beaupre, Chief Medical Officer, IDEAYA Biosciences. 

"Treatment with darovasertib as a neoadjuvant therapy provides an opportunity to save the patient's eye by avoiding enucleation or to reduce the tumor in the eye and enable treatment with less radiation to preserve vision. As an adjuvant therapy, the goal is to potentially extend recurrence free survival,", said Sreenivasa R. Chandana, M.D., Ph.D., Medical Oncologist at The Cancer & Hematology Centers in Grand Rapids, Michigan, and an investigator of the Phase 2 clinical trial. 

IDEAYA's Phase 2 clinical trial, designated as IDE196-009 (NCT05907954), is evaluating darovasertib as monotherapy in (neo)adjuvant uveal melanoma with potential near-term clinical neoadjuvant endpoints such as eye preservation for large ocular tumors and reduction in radiation dose and/or vision preservation for small or medium ocular tumors.

Pursuant to the clinical protocol, neoadjuvant treatment of primary UM patients will occur prior to a standard-of-care primary interventional treatment – typically enucleation or radiation therapy. One cohort of UM patients with large tumors will be treated with single-agent darovasertib until maximum benefit or six months, at which time they will undergo a primary interventional treatment. The neoadjuvant endpoint for this large-sized tumor cohort is eye preservation. For example, a patient who would otherwise have undergone enucleation would instead be eligible for radiation treatment. Another neoadjuvant cohort of UM patients with small or medium tumors will be treated with single-agent darovasertib until maximum benefit or six months, at which time they will undergo a primary interventional treatment such as radiation therapy. Neoadjuvant endpoints for this small- or medium-sized tumor cohort include reducing the radiation dose that the patient receives, relative to the radiation dose they would have otherwise received without the neoadjuvant treatment, and functional vision preservation.

In the adjuvant setting, each of the two neoadjuvant cohorts will be treated with single-agent darovasertib for up to six months as follow-up adjuvant therapy after the primary interventional treatment. The adjuvant endpoints for this portion of the clinical trial include recurrence free survival and useful vision.

IDEAYA plans to enroll patients in the company-sponsored Phase 2 clinical trial at clinical sites in the United States, Canada, , Europe and Australia. This clinical trial supplements and expands the scope of the ongoing investigator-sponsored Phase 1 clinical trial (IST) in Australia captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM). The NADOM trial is being led by principal investigator Professor Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent's Hospital in Sydney with participating sites of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne. IDEAYA plans to present an update of clinical data update in the fourth quarter of 2023 from the ongoing NADOM IST evaluating darovasertib as neoadjuvant therapy in primary UM.

Uveal melanoma is a rare, lethal form of melanoma that arises from melanocytes of the iris, the ciliary body, or most commonly the choroid, with an annual potential incidence of approximately 8,700 patients and an estimated prevalence of approximately 100,000 patients total in the U.S. and Europe. Current approaches for treatment of primary UM includes radiotherapy (plaque brachytherapy or stereotactic radiosurgery) and, for larger tumors, enucleation of the eye, with consequential patient impact including reduced vision, decreased depth perception, diminished social functioning and unsatisfactory cosmesis. 

Darovasertib (IDE196) is a potent, selective small molecule inhibitor of protein kinase C (PKC). Mutations in GNAQ or GNA11 (GNAQ/11) have been identified in approximately 90% of patients with metastatic UM. These mutations are associated with activation of signaling pathways, including oncogenic RAS/RAF/MEK/ERK via PKC activation, driving tumor progression. 

The FDA has designated darovasertib as an Orphan Drug in uveal melanoma, including primary and metastatic disease under 21 C.F.R Part 316. IDEAYA owns or controls all commercial rights in darovasertib in UM, subject to certain economic obligations pursuant to its exclusive, worldwide license with Novartis.

About IDEAYA Biosciences
IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets. 

Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to (i) the timing and content of a darovasertib clinical program update, (ii) the potential therapeutic benefit of darovasertib and (iii) the enrollment of study subjects in certain geographies. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Quarterly Report on Form 10-Q filed on August 10, 2023 and any current and periodic reports filed with the U.S. Securities and Exchange Commission.

Investor and Media Contact
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SOURCE IDEAYA Biosciences, Inc.