Dosing, enrollment progress in phase 1/2 study of ONCT-534 in mCRPC

Patient enrollment and dosing continue to progress in the phase 1/2 ONCT-534-101 trial (NCT05917470) of ONCT-534, a dual-action androgen receptor inhibitor under investigation for the treatment of patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC), according to a news release from Oncternal Therapeutics, the developer of the therapy.¹

In October 2023, the FDA granted a fast track designation to ONCT-534 for the treatment of patients with relapsed/refractory mCRPC that is resistant to approved ARPIs.

According to the company, all patients have now been enrolled in cohort 6 of the trial, and dosing has begun at the dose level of 1200 mg taken orally once daily. The decision to proceed to the dose level of 1200 mg was made by the study’s Safety Review Committee upon evaluating data from cohort 5 of the study, which dosed patients at 600 mg once daily.

Oncternal plans to share initial safety and efficacy data from the trial in the third quarter of 2024, which will include data from cohort 6 of the study. 

“We are encouraged by the rapid enrollment in the dose escalation portion of our phase 1/2 study with ONCT-534. The drug has been well tolerated, with no dose limiting toxicities observed to date. Patient demand continues to be strong,” said Salim Yazji, MD, chief medical officer at Oncternal Therapeutics, in the news release.¹ “We are looking forward to sharing initial safety and efficacy data soon, which will include a larger, more robust set of clinical and biomarker results, as well as longer follow-up from the earlier dosing cohorts.”

Overall, the open-label, single-arm, multicenter, phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ONCT-534 in patients with mCRPC and relapsed/refractory disease after receiving treatment with 1 or more next-generation androgen receptor pathway inhibitors (ARPIs), consisting of enzalutamide (Xtandi), abiraterone acetate (Zytiga), apalutamide (Erleada), and darolutamide (Nubeqa).

Across phase 1 and 2, the study plans to enroll a total of 59 patients throughout clinical trial sites in the US. In the phase 1 portion of the trial, approximately 27 patients will be assigned to receive ONCT-534 orally as a single agent administered daily at either the dose level of 40 mg, 80 mg, 160 mg, 300 mg, 600 mg, or 1200 mg. Based on results with these dose levels, there will be 2 recommended dose levels chosen for the phase 2 portion of the study. In this phase, approximately 32 patients will be enrolled to receive ONCT-543 daily via oral tablets at 1 of the 2 selected dose levels.

To be eligible for enrollment in the trial, patients must have an ECOG performance status of 0, 1, or 2; a serum testosterone level less than 50 ng/dL; and a life expectancy of at least 6 months. Additionally, patients’ prostate-specific antigen (PSA) level must be at last 10 ng/mL, or at least 2 ng/mL if they also have had at least a 50% increase from their lowest PSA level on prior therapy. Patients are not eligible for enrollment if they have small cell prostate cancer or neuroendocrine disease histology, including mixed histology, or if they have brain or central nervous system metastases.²

The primary end points for the trial include the determination of a maximum-tolerated dose, safety and tolerability, the proportion of patients who achieve at least a 50% PSA decline, the proportion of patients who achieve at least a 90% PSA decline, and progression-free survival.

Final study completion is expected in January 2028.²

In October 2023, the FDA granted a fast track designation to ONCT-534 for the treatment of patients with relapsed/refractory mCRPC that is resistant to approved ARPIs.³ Fast track designation is awarded to new drugs and vaccines that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. With this designation, the development process for ONCT-534 can benefit from more frequent engagement with the FDA, eligibility for accelerated approval, and priority review.

References

1. Oncternal announces enrollment completed and dosing initiated for sixth dose cohort of phase 1/2 study of ONCT-534 for the treatment of R/R metastatic castration-resistant prostate cancer. News release. Oncternal Therapeutics. Published online and accessed July 15, 2024. https://investor.oncternal.com/news-releases/news-release-details/oncternal-announces-enrollment-completed-and-dosing-initiated-0

2. A clinical study of ONCT-534 in subjects with metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Last updated April 17, 2024. Accessed April 19, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05917470

3. Oncternal Therapeutics announces FDA granted fast track designation for ONCT-534 for the treatment of metastatic castration-resistant prostate cancer. News release. Oncternal Therapeutics. October 26, 2023. Accessed July 15, 2024. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-announces-fda-granted-fast-track