Treatment begins in study of gedatolisib plus darolutamide in mCRPC

The first patient has been dosed in the phase 1b/2 CELC-G-201 trial (NCT06190899), assessing gedatolisib in combination with darolutamide (Nubeqa) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a next-generation androgen receptor (AR) inhibitor, according to a news release by Celcuity, the developer of the therapy.¹

Primary completion of the study is expected in 2025.

Gedatolisib is a potent, reversible dual inhibitor that selectively targets all class 1 isoforms of PI3K and mTORC1/2. According to Celcuity, the mechanism of action and pharmacokinetic properties of gedatolisib are differentiated from other currently approved therapies that target PI3K, mTOR, or both.

“Evaluating a PAM inhibitor, such as gedatolisib, in combination with a next generation androgen receptor, has strong scientific rationale and is an important priority for mCRPC research. As it stands, there are limited options for patients with mCRPC whose disease progressed on or after treatment with an androgen receptor inhibitor. Gedatolisib’s differentiated mechanism of action, and comprehensive blockade of the PAM pathway, may provide an additional treatment option for these patients,” said Karim Fizazi, MD, PhD, in a news release on the study.¹ Fizazi is a medical oncologist at Institut Gustave Roussy and a professor of oncology at the University of Paris Saclay in Villejuif, France

Overall, the open-label, randomized CELC-G-201 trial is assessing the safety, preliminary efficacy, and pharmacokinetics of gedatolisib plus darolutamide in mCRPC. Patients will be enrolled across clinical trial sites in the US and Europe.

The primary objectives for the phase 1b portion of the study are safety and tolerability with the combination, as well as the determination of a recommended dose level for phase 2 of the study. The primary end point for the phase 2 portion of the trial is radiographic progression-free survival (rPFS) at 6 months following receipt of the recommended phase 2 dose (RP2D). Secondary end points for the phase 2 portion of the study are rPFS at 12 months and the objective response rate.²

In total, the study plans to enroll 48 to 54 adult patients with mCRPC who have progressed after prior treatment with an AR inhibitor. It is expected that 36 patients will be randomly assigned to receive 600 mg darolutamide plus either 120 mg gedatolisib in arm 1, or 180 mg gedatolisib in arm 2, during phase 1 of the study. For the phase 2 portion of the trial, the additional participants will be enrolled for a total evaluation of 30 participants treated at the RP2D level.

Inclusion criteria for the study includes having histologically or cytologically confirmed adenocarcinoma of the prostate, presence of metastatic disease identified via conventional imaging, previous treatment with an AR inhibitor 4 or more weeks prior to the study and progression following treatment, and having continued primary androgen deprivation therapy with luteinizing hormone-releasing hormone analog if the patient had not undergone bilateral orchiectomy. Additionally, patients must have recovered from toxicities related to any prior treatments, an ECOG performance score of 1 or lower, and adequate bone marrow, hepatic, renal, and coagulation function.³

“We are excited to begin enrolling patients in our 201 trial and advancing towards our ultimate goal of providing a transformative therapeutic option for patients with prostate cancer,” said chief medical officer of Celcuity Igor Gorbatchevsky, MD, in the news release.¹ “A significant unmet need remains for patients with metastatic castration resistant prostate cancer who have become resistant to a next generation androgen receptor inhibitor.”

Primary completion of the study is expected in 2025.

References

1. Celcuity announces first patient dosed in phase 1b/2 CELC-G-201 clinical trial of gedatolisib for the treatment of metastatic castration resistant prostate cancer. News release. Celcuity Inc. February 22, 2024. Accessed February 23, 2024. https://www.globenewswire.com/news-release/2024/02/22/2834087/0/en/Celcuity-Announces-First-Patient-Dosed-in-Phase-1b-2-CELC-G-201-Clinical-Trial-of-Gedatolisib-for-the-Treatment-of-Metastatic-Castration-Resistant-Prostate-Cancer.html

2. A prostate cancer study. Celcuity. https://www.celcuity.com/clinical-trials/celc-g-201-prostate-cancer/

3. Gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Last updated January 5, 2024. Accessed February 23, 2024. https://clinicaltrials.gov/study/NCT06190899