Darovasertib, in combination with crizotinib, more than doubled progression-free survival in a registrational trial, leading Truist analysts to declare a “best-in-class efficacy profile” for the PKC inhibitor.
IDEAYA Biosciences and Servier’s metastatic eye cancer candidate more than doubled median progression-free survival in a registrational trial, paving its way to the FDA in the second half of this year.
“Idea crystallized,” Truist Securities declared in a Monday morning note to investors, adding that Darovasertib, a selective small molecule PKC inhibitor, demonstrated a best-in-class efficacy profile.
IDEAYA’s stock was up 21% in premarket trading on Monday, trading at just over $37.
In the Phase 2/3 OptimUM-02 trial of patients with metastatic uveal melanoma, Darovasertib combined with crizotinib met the primary endpoint of statistically significant improvement in progression-free survival (PFS), the companies announced Monday. The therapy elicited PFS of 6.9 months compared to 3.1 months for patients who received the investigator’s choice of therapy (ICT).
The overall response rate for patients treated with darovasertib plus crizotinib was 37.1% vs. 5.8% for the ICT group, with five patients enjoying a complete response. ORR is a secondary endpoint of the trial.
The trial is investigating the combo as a first line treatment in 210 patients with HLA-A*A2:01-negative metastatic uveal melanoma compared to an ICT arm “reflective of real-world clinical practice” comprising 103 patients. The ICT arm included 78 patients taking Bristol Myers Squibb’s anti-CTLA-4/PD-1 tandem Yervoy plus Opdivo and 25 participants on Merck’s immuno-oncology juggernaut Keytruda.
Darovasertib was well-tolerated, with a “manageable safety profile” consistent with previously reported adverse events, according to IDEAYA and Servier’s press release.
With these results in hand, the partners plan to submit a new drug application for Darovasertib in the second half of this year.
The results were “largely in line with most investor expectations,” Leerink Partners wrote in a Monday morning note, and closely matched those of the Phase 1/2 OptimUM-01 trial, in which darovasertib elicited 7 months of median PFS.
“We think some investors had anticipated successful results with the hope that the mPFS would be superior to that seen in the Ph 1/2 in order to maintain the momentum exiting the topline announcement,” Leerink wrote. “As such, IDYA now becomes a commercial ‘show-me’ story,” driven by price and how much of the HLA-A2*02:01 positive population darovasertib can capture.
“We see daro’s eventual positioning as the new potential standard of care” in first line HLA‑A2(-) metastatic uveal melanoma, Truist analysts wrote, projecting around $800 million peak revenue in this indication.
Meanwhile, darovasertib could be competing with Immunocore’s Kimmtrak in HLA-A2*02:01 positive uveal melanoma, an indication that IDEAYA also intends to pursue, according to Leerink. Kimmtrak won approval in this indication in January 2022. If darovasertib does capture a portion of these patients, “it would be upside to our estimates of $415 million in peak revenues in the HLA-A*02:01-negative population,” the analysts said.
There are currently no FDA-approved systemic therapies for primary positive uveal melanoma or for patients with HLA-A*02:01-negative metastatic uveal melanoma, according to Monday’s press release.
