On April 16, 2021 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a synthetic lethality-focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported clinical data from the ongoing Phase 1/2 trial evaluating darovasertib (IDE196) monotherapy and binimetinib combination therapy in patients with solid tumors, including Metastatic Uveal Melanoma (MUM) and Skin Melanoma (ClinicalTrials.gov Identifier: NCT03947385) (Press release, Ideaya Biosciences, APR 16, 2021, View Source [SID1234578132]).
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"The darovasertib single-agent one-year survival data in MUM is encouraging and compares favorably to historical survival rates in this indication, where a therapy has yet to be approved," said Meredith McKean, MD, MPH, Associate Director, Melanoma and Skin Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN. "The early partial responses observed in the darovasertib and binimetinib combination in MUM are exciting where historical response rates have been from zero to low to mid-single-digit percent, and we look forward to seeing the data set mature," said Richard Carvajal, MD, Co-Leader, Precision Oncology and Systems Biology Program, Director of Experimental Therapeutics and Director of the Melanoma Service, Columbia University Irving Medical Center.
Darovasertib Monotherapy Clinical Efficacy in Solid Tumors
There have been 81 darovasertib monotherapy BID MUM and 7 Skin Melanoma patients enrolled across the IDEAYA and Novartis Phase 1/2 clinical trials at the time of data and analyses cutoff on April 13th, 2021, with an aggregate of 88 patients evaluable for safety and 81 evaluable for efficacy based on RECIST 1.1. Reported data is preliminary and based on an unlocked database. Evaluation and follow-up of the monotherapy arm of the clinical trial continues.
Darovasertib Monotherapy Preliminary Results Summary
57% 1-Year Overall Survival (OS) Rate was observed in predominantly second line, third line and heavily pre-treated (out to 7 and 8 lines of prior treatment) Metastatic Uveal Melanoma (MUM) patients with 95% CI (44%, 69%); Historical 1-Year OS Rate in similar MUM populations has been reported at 37% (Source: Rantala 2019, Immunocore March 2021 presentation, Synthetic Control Arm, 2+ L)
Median OS of 13.2 months was observed in predominanantly second line, third line and heavily pre-treated (out to 7 and 8 lines of prior treatment) MUM patients with 95% CI (10.7 months, Not Reached); Historical median OS in similar MUM populations has been reported at approximately 7 months (Source: Rantala 2019, Immunocore March 2021, Synthetic Control Arm, 2+ L)
61% (n=46) of MUM patients out of 75 evaluable had tumor reduction per RECIST 1.1. evaluation, including 15 patients (20%) with >30% target lesion reduction and one confirmed complete response. In the Skin Melanoma cohort, 80% (n=4) of evaluable patients (n=5) had tumor reduction per RECIST 1.1. evaluation, including one confirmed partial response
Darovasertib Monotherapy Clinical Safety
Overall safety profile of darovasertib monotherapy is consistent with prior reports (Ref. 2019 AACR (Free AACR Whitepaper)) and includes primarily common low grade but manageable GI toxicities and hypotension.
Preliminary Darovasertib and Binimetinib Combination Clinical Efficacy in MUM
The combination of darovasertib plus binimetinib is being evaluated pursuant to a clinical trial collaboration and drug supply agreement with Pfizer, which the companies have amended to support a target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm in MUM. At the time of the data and analyses cutoff on April 13th, 2021, twenty four MUM patients have enrolled in the darovasertib and binimetinib combination study, including 8 patients dosed in the Phase 1/2 dose expansion cohort of the combination study. Reported data is preliminary and based on an unlocked database. Enrollment in the darovasertib and binimetinib combination arm of the clinical trial is ongoing.
Darovasertib and Binimetinib Combination Therapy Preliminary Data Summary
2 partial responses observed out of nine MUM patients with at least 2 post-baseline scans (22%) by RECIST 1.1 guidelines, including 1 confirmed partial response and 1 unconfirmed partial response (-40.5%) awaiting a confirmatory scan
79% of evaluable MUM patients with at least 1 post-baseline scan show tumor reduction; follow-up for overall response is still immature
Combination doses for Phase 1/2 dose expansion have been selected based on anticipation of activity and overall tolerability in a larger treatment cohort
Treatment-related adverse events observed in the darovasertib and binimetinib combination arm in MUM primarily include: nausea, vomiting, diarrhea, rash, edema, AST/ALT increase and CK increase (>10%); and hypotension (<10%)
IDEAYA’s clinical development strategy in MUM is focused on darovasertib combinations, including with binimetinib, a MEK inhibitor, and in a separate clinical study with crizotinib, a cMET inhibitor, each pursuant to the clinical trial collaboration and drug supply agreement with Pfizer.
Darovasertib Investor Day Webcast
IDEAYA will host an investor webcast with a presentation at 8:00 a.m. ET today. A link to the webcast and a copy of the presentation is posted on the Investor Relations Events section of the Company’s website at View Source The update may also be accessed by dialing 1-866-248-8441 (domestic) or 1-720-452-9102 (international) five minutes prior to the start of the call and providing the passcode 2793795. An archived replay of the webcast will be accessible for 90 days following the event.
Meredith McKean, MD, MPH, Associate Director, Melanoma and Skin Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN, and Richard Carvajal, MD, Co-Leader, Precision Oncology and Systems Biology Program, Director of Experimental Therapeutics and Director of the Melanoma Service, Columbia University Irving Medical Center, will participate in the webcast.