Skip to main content
Journal cover image

Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.

Publication ,  Journal Article
Shah, PD; Wethington, SL; Pagan, C; Latif, N; Tanyi, J; Martin, LP; Morgan, M; Burger, RA; Haggerty, A; Zarrin, H; Rodriguez, D; Domchek, S ...
Published in: Gynecol Oncol
November 2021

OBJECTIVE: Platinum-resistant, high-grade serous ovarian cancer (HGSOC) has limited treatment options. Preclinical data suggest that poly(ADP-ribose) polymerase inhibitors (PARPi) and ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) are synergistic. CAPRI (NCT03462342) is an investigator-initiated study of olaparib plus ceralasertib in recurrent HGSOC. Herein, we present results from the platinum-resistant cohort. METHODS: A Simon 2-stage design was utilized. Platinum-resistant HGSOC patients received ceralasertib 160 mg orally daily, days 1-7 and olaparib 300 mg orally twice daily, days 1-28 of a 28-day cycle until toxicity or progression. Primary endpoints were toxicity and efficacy including objective response rate (ORR) by RECIST. Secondary endpoint was progression-free survival (PFS). The null hypothesis (≤5% ORR) would be rejected if there were ≥ 1 responses in 12 patients. RESULTS: Fourteen PARPi-naïve patients were evaluable for toxicity; 12 were evaluable for response. Three had BRCA1 mutations (1 germline, 2 somatic). Adverse events possibly related to treatment were primarily grade (G) 1/2. G3 toxicities included nausea (14.3%), fatigue (7.1%), anorexia (7.1%), and anemia (7.1%). No objective responses occurred. Best response was stable disease in 9 patients and progressive disease in three. Five patients had a ≥ 20% to <30% reduction in disease burden, including 3 with BRCA1 mutations. Three of 11 patients (27%; 2 with BRCA1 mutations) evaluable by Gynecologic Cancer Intergroup criteria had >50% CA-125 decline, including 2 with CA-125 normalization. Median PFS was 4.2 months overall (90% CI:3.5-8.2) and 8.2 months (3.6 months-not determined) for patients with BRCA1 mutations. CONCLUSIONS: Olaparib plus ceralasertib is well-tolerated. No objective responses occurred, though a signal of activity was seen particularly in disease associated with BRCA1. Further evaluation of this combination should include alternate dosing strategies in genomically-selected populations.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

November 2021

Volume

163

Issue

2

Start / End Page

246 / 253

Location

United States

Related Subject Headings

  • Tomography, X-Ray Computed
  • Sulfonamides
  • Response Evaluation Criteria in Solid Tumors
  • Pyrimidines
  • Protein Kinase Inhibitors
  • Progression-Free Survival
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Piperazines
  • Phthalazines
  • Ovary
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shah, P. D., Wethington, S. L., Pagan, C., Latif, N., Tanyi, J., Martin, L. P., … Simpkins, F. (2021). Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer. Gynecol Oncol, 163(2), 246–253. https://doi.org/10.1016/j.ygyno.2021.08.024
Shah, Payal D., Stephanie L. Wethington, Cheyenne Pagan, Nawar Latif, Janos Tanyi, Lainie P. Martin, Mark Morgan, et al. “Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.Gynecol Oncol 163, no. 2 (November 2021): 246–53. https://doi.org/10.1016/j.ygyno.2021.08.024.
Shah PD, Wethington SL, Pagan C, Latif N, Tanyi J, Martin LP, et al. Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer. Gynecol Oncol. 2021 Nov;163(2):246–53.
Shah, Payal D., et al. “Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.Gynecol Oncol, vol. 163, no. 2, Nov. 2021, pp. 246–53. Pubmed, doi:10.1016/j.ygyno.2021.08.024.
Shah PD, Wethington SL, Pagan C, Latif N, Tanyi J, Martin LP, Morgan M, Burger RA, Haggerty A, Zarrin H, Rodriguez D, Domchek S, Drapkin R, Shih I-M, Smith SA, Dean E, Gaillard S, Armstrong D, Torigian DA, Hwang W-T, Giuntoli R, Simpkins F. Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer. Gynecol Oncol. 2021 Nov;163(2):246–253.
Journal cover image

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

November 2021

Volume

163

Issue

2

Start / End Page

246 / 253

Location

United States

Related Subject Headings

  • Tomography, X-Ray Computed
  • Sulfonamides
  • Response Evaluation Criteria in Solid Tumors
  • Pyrimidines
  • Protein Kinase Inhibitors
  • Progression-Free Survival
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Piperazines
  • Phthalazines
  • Ovary