Trial expands to evaluate ORIC-944 with AR inhibitors in prostate cancer

ORIC Pharmaceuticals has entered into clinical collaborations with Bayer and Janssen Research & Development, LLC, to expand their phase 1b trial (NCT05413421) of ORIC-944 to include combination cohorts of the therapy with darolutamide (Nubeqa) and apalutamide (Erleada) in patients with metastatic prostate cancer, ORIC announced in a news release.¹

The phase 1b monotherapy trial enrolled 42 adult patients with metastatic prostate cancer.

According to ORIC, the trial began dosing the first patients enrolled in the combination cohorts in the first half of 2024. Both cohorts include a dose escalation and a dose expansion phase. Under the agreement, ORIC maintains full global development and commercial rights to ORIC-944, and Bayer and Janssen have agreed to supply darolutamide and apalutamide, respectively, for the trial.

ORIC-944 is an investigational “potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2),” according to the company.¹ The therapy was initially being evaluated as a monotherapy in the phase 1b trial.

Data on ORIC-944 was recently presented at the 2024 American Association of Cancer Research Annual Meeting in April 2024. Overall, ORIC-944 demonstrated tumor growth inhibition in prostate cancer xenograft models, a clinical half-life of approximately 20 hours, and a favorable safety profile. Additionally, in preclinical combination studies, ORIC-944 enhanced AR pathway inhibitor anti-tumor activity and demonstrated in vitro and in vivo synergy.²

“We are pleased to enter into these clinical collaborations to investigate the broader potential of ORIC-944 in combination with AR inhibitors, a combination approach that we believe is particularly promising based on our preclinical findings as well as emerging clinical data,” said Jacob M. Chacko, MD, president and chief executive officer of ORIC Pharmaceuticals, in the news release.¹ “As reported at the AACR Annual Meeting earlier this year, the combination of ORIC-944 and AR inhibitors demonstrated synergy in multiple prostate cancer models with a unique mechanism of reprogramming prostate cancer to revert to an AR-dependent state. Together with the emerging clinical profile of ORIC-944, which has already demonstrated superior clinical half-life, robust target engagement and favorable safety as a monotherapy, the combination of ORIC-944 with an AR inhibitor has the potential to become a novel treatment paradigm for patients with prostate cancer.”

In total, the phase 1b monotherapy trial enrolled 42 adult patients with metastatic prostate cancer across clinical trial sites in the US. Patients included in the study received ORIC-944 orally once daily for 28 days.³

To be eligible for enrollment, patients needed to have metastatic prostate cancer, evidence of progressive disease, an ECOG performance score of 0 or 1, and adequate organ function. Patients were excluded from the study if they had a history or presence of CNS metastases, known HIV infection, active symptomatic Hepatitis B or C infection, or active gastrointestinal disease or other malabsorption syndromes. Additionally, patients could not have a history of class 3 or 4 congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within 6 months prior to enrollment.

The primary outcome measures included the determination of a recommended phase 2 dose, the maximum plasma concentration, time to maximum observed concentration, area under the curve, and the apparent plasma terminal elimination half-life. Secondary end points were the clinical benefit rate, the objective response rate, the duration of response, and progression-free survival.

References

1. Multiple clinical collaborations with strategic partners to support ongoing trial evaluating ORIC-944 in combination with AR inhibitors for the treatment of prostate cancer. News release. ORIC Pharmaceuticals. July 16, 2024. Accessed July 17, 2024. https://investors.oricpharma.com/news-releases/news-release-details/oric-pharmaceuticals-announces-multiple-clinical-collaborations

2. Marx MA, Burns AC, Arora N, et al. Discovery of ORIC-944, a novel inhibitor of PRC2 with best-in-class properties for the treatment of prostate cancer. Presented at: 2024 American Association of Cancer Research Annual Meeting. April 5 – 10, 2024. San Diego, California. Abstract ND04. Accessed July 17, 2024. https://aacrjournals.org/cancerres/article/84/7_Supplement/ND04/742761/Abstract-ND04-Discovery-of-ORIC-944-a-novel

3. Study of ORIC-944 in patients with metastatic prostate cancer. ClinicalTrials.gov. Last updated May 3, 2023. Accessed July 17, 2024. https://clinicaltrials.gov/study/NCT05413421