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Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.
- Source :
-
Gynecologic Oncology . Nov2021, Vol. 163 Issue 2, p246-253. 8p. - Publication Year :
- 2021
-
Abstract
- 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. 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. 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. 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. • Combination olaparib and ceralasertib is tolerable at the current RP2D. • No RECIST radiological responses occurred and PFS was 4.2 months. • PFS was 8.2 months in 3 subjects with BRCA1 mutations. • CA-125 responses by GCIG criteria were seen in 3 of 11 evaluable subjects. • A signal of activity was seen in DNA repair deficient platinum resistant HGSOC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00908258
- Volume :
- 163
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Gynecologic Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 153322785
- Full Text :
- https://doi.org/10.1016/j.ygyno.2021.08.024