The partial clinical hold was put on the phase 1/2 VELA study after visual adverse events were observed in some patients with solid tumors after treatment with BLU-222.
The FDA has placed a partial clinical hold on the phase 1/2 VELA trial (NCT05252416) evaluating BLU-222 in patients with solid tumors, according to Blueprint Medicines Corporation.1
The hold clinical hold was placed because of visual adverse events (AEs) seen in some patients, including transient, reversible episodes of light sensitivity, and blurred vision. Besides 1 grade 3 AE involving light sensitivity and blurred vision in a patient treated at 600 mg twice daily, AEs were all grade 1.
All AEs resolved with dose interruption or reduction and there have been no treatment-emergent abnormal findings observed in patients who have been given detailed ophthalmologic examinations.
Currently enrolled patients will continue treatment with BLU-222 while additional patients will not be enrolled until the partial clinical hold is lifted.
"Patient safety is our first priority, and we are working closely with the FDA to investigate the reported visual adverse events as well as amend the VELA trial protocol to provide specific guidance to investigators on how to monitor for and manage these events should they occur," said Becker Hewes, MD, chief medical officer at Blueprint Medicines, in the press release. "We have confidence in the benefit-risk profile of BLU-222 based on the activity and safety data we have seen to date in the dose escalation study. In addition, we recognize the urgency to treat patients with CDK2-vulnerable cancers, many of whom have seen their disease progress after exhausting all other options, and we aim to resume enrollment as expeditiously and responsibly as possible."
Investigators in the international, open-label, first-in-human, phase 1/2 VELA trial are assessing safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of the selective inhibitor of CDK2, BLU-222.2
In this dose-escalation portion of the VELA trial, patients have been treated with BLU-222 at doses ranging from 50 mg twice a day to 800 mg twice a day. So far, there has been evidence of clinical benefit observed with BLU-222 at these doses and there have been no discontinuations due to AEs.
Primary end points of the phase 1 portion of the trial are to determine the maximum tolerated dose and recommended phase 2 dose of BLU-222 and assess the rate and severity of AEs. Secondary end points include overall response rate, to assess treatment-induced modulation of cyclin E/CDK2 pathway biomarkers, duration of response, disease control rate, PK, PD, clinical benefit rate, progression-free survival, and overall survival.
Patients aged 18 years and older with advanced solid tumors that have progressed beyond standard of care, patients with estrogen receptor-positive/ HER2-negative breast cancer ER-positive that has progressed following treatment with a CDK4/6 inhibitor, endometrial and gastric cancer that has progressed after at least 2 prior therapies, including 1 prior platinum therapy, or platinum refractory or platinum resistant ovarian cancer CCNE1 amplified tumors that have progressed beyond treatment with the standard of care.
Consistent with prior guidance, initial data from the dose-escalation portion of the VELA trial are expected to be released in early 2023.