Results from a phase 2 study demonstrated that ceralasertib plus olaparib was well tolerated and demonstrated promising clinical activity among patients with recurrent platinum-sensitive ovarian cancer, regardless of tumor genomic instability. 

These data will be presented by Fiona Simpkins, MD, Penn Medicine Abramson Cancer Center, Philadelphia, Pennsylvania, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

In this open-label study, 37 patients with platinum-sensitive ovarian cancer with tumors exhibiting either germline homologous recombination (HR) gene mutations (n = 3), genomic instability (n = 10; 8 HRD positive, 2 LOH high), no genomic instability (n = 19), or tumors of unknown status (n = 5) were enrolled to receive 160 mg of ceralasertib (once daily on days 1 to 7) plus 300 mg of olaparib (twice daily on days 1 to 28) in 28 day cycles until disease progression or unacceptable toxicity. Patients were permitted to have undergone prior PARPi therapy and there was no limit to the number of prior regimens. Primary end points included objective response rate (ORR) and toxicity. A key secondary end point was progression-free survival (PFS). 

At analysis, patients received a median of 8 cycles. In the intention-to-treat population, ORR was 48.5% and median PFS was 8.3 months with 3 complete responses and 13 partial responses. In patients without genomic instability, ORR was 43.8% and median PFS was 7.6 months with 1 complete response and 6 partial responses. In patients with genomic instability, ORR was 40% and median PFS was 8.3 months with 4 partial responses. In patients with germline HR gene mutations, ORR was 100% and median PFS was not achieved with 1 complete response and 2 partial responses. In patients with unknown genomic instability, ORR was 50% with 1 complete response and 1 partial response. 

Grade 3 toxicities were experienced by 40.5% of patients, the most common including anemia (21.6%) and diarrhea (5.4%). Grade 4 thrombocytopenia was experienced by 5.4% of patients. Dose reductions occurred in 37.8% of patients and 1 patient discontinued treatment due to fatigue and nausea (grade 2). 

As study authors concluded, ceralasertib plus olaparib “was well tolerated and active in pts with platinum sensitive HGSOC warranting further evaluation.” 

Source: 

Simpkins F, Nasioudis D, Wethington SL, et al. Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-sensitive epithelial ovarian cancer (cohort A).  Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract #5510