FDA Lifts Partial Hold on VELA Trial Evaluating BLU-222 in Advanced Solid Tumors

Blueprint Medicines announced on March 28, 2023, that the FDA has removed a partial clinical hold on the phase 1/2 VELA trial (NCT05252416) trial of BLU-222.¹ The agency discontinued enrollment on February 10, 2023, due to transient, reversible episodes of light sensitivity and blurred vision reported in a limited number of patients, but allowed already enrolled patients to continue receiving the investigational CDK2 inhibitor.²

Blueprint is working with trial sites to reinitiate patient enrollment.

“With a focus on patient safety, we have worked diligently with the FDA over the last several weeks to resolve the partial clinical hold by updating adverse event monitoring and management procedures. We will now collaborate closely with investigators to resume patient enrollment,” Becker Hewes, MD, Blueprint’s chief medical officer, said in a news release. “We are confident in the potential of BLU-222 to improve outcomes in patients with cancers vulnerable to CDK2 inhibition, and we look forward to presenting initial dose escalation data from the VELA trial in the second quarter of 2023.”

BLU-222 is an oral, investigational, potent, selective CDK2 inhibitor currently under evaluation in the phase 1 dose-escalation portion of the first-in-human, open-label VELA trial. Investigators are assessing BLU-222 for safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of the agent in adults with CCNE1-amplified tumors or estrogen receptor–positive, HER2-negative breast cancer following progression on a CDK4/6 inhibitor.

To date, patients have been treated at doses from 50 mg twice daily to 800 mg twice daily, with evidence of clinical benefit and no discontinuations due to adverse effects (AEs). In preclinical studies, the agent demonstrated potent CDK2 inhibition and antitumor activity, and tumor regression in combination with carboplatin and paclitaxel.³

Preliminary visual AEs included transient, reversible episodes of light sensitivity and blurred vision. Most events were grade 1, except for 1 grade 3 event involving light sensitivity and blurred vision in a patient treated at 600 mg twice daily. All events resolved with dose interruption or reduction. Investigators observed no treatment-emergent abnormal findings, including uveitis, in patients who have undergone thorough ophthalmologic exams.

References

1. Blueprint Medicines announces lift of partial clinical hold on phase 1/2 VELA trial of BLU-222. News release. Blueprint Medicines Corporation. March 28, 2023. Accessed March 29, 2023. https://ir.blueprintmedicines.com/news-releases/
2. Blueprint Medicines announces partial clinical hold for phase 1/2 VELA trial of BLU-222. News release. Blueprint Medicines Corporation. February 10, 2023. Accessed March 29, 2023. https://ir.blueprintmedicines.com/
3. Brown V, Ramsden P, House N, et al. BLU-222, an investigational, potent, and selective CDK2 inhibitor, demonstrated robust antitumor activity in CCNE1-amplified ovarian cancer models. Cancer Res. 2022;82(suppl 12):2306. doi:10.1158/1538-7445.AM2022-2306