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LB006/#1568  Neoadjuvant niraparib monotherapy in homologous recombination deficiency-positive advanced ovarian cancer: a prospective, multicenter, single-arm, phase II study (NANT)
  1. Huayi Li1,
  2. Dan Liu1,
  3. Wei Zhang1,
  4. Ping Wang2,
  5. Jundong Li3,
  6. Wanying Shan1,
  7. Ronghua Liu1,
  8. Gang Chen1,
  9. Mingfu Wu1,
  10. Xiao Li4,
  11. Cheng Liu5,
  12. Rutie Yin2,
  13. Shengtao Zhou2,
  14. Maomao Li2,
  15. Shanyang He6,
  16. Guangnian Zhao1,
  17. Kun Song4,
  18. Li Hong5,
  19. Ding Ma1 and
  20. Qinglei Gao1
  1. 1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Gynecologic Oncology, Wuhan, China
  2. 2West China Second University Hospital, Sichuan University, Department of Gynecology and Obstetrics, Chengdu, China
  3. 3Sun Yat-sen University Cancer Center, Sun Yat-sen University, Department of Gynecological Oncology, Guangzhou, China
  4. 4Qilu Hospital of Shandong University, Shandong University, Department of Obstetrics and Gynecology, Jinan, China
  5. 5Renmin Hospital of Wuhan University, Department of Obstetrics and Gynecology, Wuhan, China
  6. 6Guangdong Provincial People’s Hospital Affiliated to Southern Medical University, Guangdong Academy of Medical Sciences, Department of Gynecology and Obstetrics, Guangzhou, China

Abstract

Introduction PARP inhibitors have been widely used as maintenance therapy in ovarian cancer management. However, their potential as neoadjuvant therapy remains unclear. Here, we report the activity and safety of neoadjuvant niraparib (NANT) monotherapy in homologous recombination deficiency (HRD)-positive high-grade serous ovarian cancer (HGSOC), and investigate cell clusters that associate with response to niraparib.

Methods Key eligibility: patients with newly diagnosed FIGO III/IV HRD-positive HGSOC and low likelihood of optimal cytoreduction or poor surgical candidates. Enrolled patients received daily oral niraparib (200 or 300 mg) for two 28-day cycles. The co-primary endpoints were objective response rate (ORR) and R0 resection rate. Cell clusters were profiled by scRNA-seq and mIHC.

Results Between January 18, 2021 and July 18, 2023, 67 patients received NANT monotherapy, 48 patients completed response evaluations, and 40 patients underwent interval debulking surgery. The ORR was 62.5% (30 PRs; table 1). The R0 resection rate was 80.0% (n=32). The GCIG CA125 response rate was 79.2% (n=38). The prevalence of CRS 3, 2, and 1 was 17.9%, 51.3%, and 30.8%, respectively. No new safety signal was observed. Grade ≥3 treatment-related adverse events occurred in 61.2% (n=41) of patients. Post-treatment eTreg cell proportion was positively correlated with CA125 concentrations and targeting eTreg cells using anti-CCR8 antibody (ZL-1218) potentiated niraparib in preclinical models (figure 1).

Abstract LB006/#1568 Table 1

Summary of response, surgical, and pathological assessments

Abstract LB006/#1568 Figure 1

Neoadjuvant Niraparib monotherapy (NANT) for HRD ovarian cancer

Conclusion/Implications NANT monotherapy achieved encouraging clinical activity and tolerable toxicities in HRD-positive HGSOC, offering an alternative option for patients unwilling to receive or unable to tolerate neoadjuvant chemotherapy (NANT study/NCT04507841). Niraparib plus anti-CCR8 antibodies is a promising combination strategy for HRD-positive HGSOC.

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