Multicenter Phase II Study of Olaparib and the ATR Inhibitor Ceralasertib in Metastatic Castration-Resistant Prostate...

Area of Science:

• Oncology
• Clinical Trials
• Prostate Cancer Research

Background:

• Preclinical data suggested synergistic antitumor effects between poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and ataxia telangiectasia-mutated and Rad3-related (ATR) inhibitor ceralasertib.
• This combination therapy was explored for potential benefits in patients with metastatic castration-resistant prostate cancer (mCRPC).

Purpose of the Study:

• To evaluate the efficacy of combining olaparib and ceralasertib in mCRPC patients.
• To assess treatment outcomes in both homologous recombination proficient (HRP) and homologous recombination repair gene mutation (HRRm) subgroups.

Main Methods:

• A clinical trial enrolled 35 HRP and 12 HRRm PARP inhibitor-naïve mCRPC patients.
• Patients received olaparib plus ceralasertib in 28-day cycles.
• Disease response rate (dRR) was the primary endpoint in HRP patients; secondary endpoints included dRR in HRRm patients, progression-free survival (PFS), and safety.

Main Results:

• A disease response rate (dRR) of 11% was observed in HRP patients (4/35).
• Four of 12 HRRm patients also responded.
• Median PFS for HRP patients was 8.2 months, with 36% experiencing Grade 3 or higher toxicity, primarily anemia.

Conclusions:

• The combination of ceralasertib and olaparib demonstrated limited activity in the HRP mCRPC population.
• The response rate in HRRm patients did not exceed that of prior studies using single-agent PARP inhibitors.