Meredith McKean, MD, Sarah Cannon Research Institute at Tennessee Oncology, Associate Director, Melanoma and Skin Cancer Research speaks about IDEAYA Reports Clinical Data from Phase 2 Expansion Dose of Darovasertib and Crizotinib Synthetic Lethal Combination in Heavily Pre-Treated Metastatic Uveal Melanoma.
IDEAYA Biosciences, Inc., a precision medicine oncology company focused on the discovery and development of targeted therapeutics, has provided a clinical data update for the Phase 1/2 trial evaluating the synthetic lethal combination of darovasertib and crizotinib in patients with metastatic uveal melanoma (MUM).
There are presently no FDA-approved medicines for metastatic uveal melanoma or GNAQ/GNA11 solid tumors, indicating that there is a significant unmet medical need. Pembrolizumab and tebentafusp (both 5%), MEK inhibitor selumetinib in conjunction with dacarbazine (3%), and cMET inhibitor cabozantinib monotherapy (0%).
Darovasertib (IDE196) is a tiny chemical that has the potential to be the first-in-class inhibitor of PKC. According to a clinical study collaboration and medication supply agreement with Pfizer, IDEAYA is evaluating the synthetic lethal combination of darovasertib and crizotinib, a small molecule cMET inhibitor. The firms have committed to fund the recruitment of about 40 patients in MUM’s ongoing Phase 1/2 clinical combo arm.
Darovasertib and Crizotinib in Combination: Clinical Data Update
Twenty-two (22) heavily pre-treated MUM patients had enrolled in the darovasertib and crizotinib combination arm at the expansion dose at the time of the data and analyses cutoff on November 25, 2021, with sixteen (16) evaluable patients who had received one or more tumor scans and six patients who were awaiting their first tumor scan. Thirteen (13) patients have had at least two tumor scans to assess potential responses. The information provided is preliminary and comes from an unlocked database. The clinical trial’s darovasertib and crizotinib combo arm is still enrolling participants.
In the expansion dose cohort of a Phase 1/2 clinical trial assessing darovasertib and crizotinib synthetic lethal combination in metastatic uveal melanoma (MUM) patients, the business saw good clinical activity.
The following is a list of the preliminary intermediate data:
16 of 16 evaluable patients with >1 post-baseline scan showed tumor shrinkage as evaluated by target lesion size reduction, resulting in a 100% Disease Control Rate (DCR). 4 of 13 patients with > 2 post-baseline scans showed a confirmed partial response (PR) as evaluated by RECIST 1.1 based on an investigator or central review, and no patients were taken off treatment prior to the second scan. One patient with an unconfirmed PR as indicated by RECIST 1.1 is awaiting a follow-up tumor scan. 46 percent of patients (6 of 13) with > 2 post-baseline scans saw >30 percent tumor decrease, including one patient with an unconfirmed PR as defined by RECIST 1.1.
These findings provide clinical proof-of-concept for the synthetic lethal combo therapy of darovasertib and crizotinib. These findings support the company’s translational research finding that reduced cMETactivity, as evaluated by gene signature score, was related to Phase 1 clinical response to darovasertib monotherapy.
You May Also Like: