Pamiparib dose escalation in Chinese patients with non-mucinous high-grade ovarian cancer or advanced triple-negative breast cancer

Cancer Med. 2021 Jan;10(1):109-118. doi: 10.1002/cam4.3575. Epub 2020 Oct 31.


Background: The recommended phase 2 dose (RP2D) of pamiparib, an investigational PARP1/2 inhibitor, was established as 60 mg twice daily (BID) in a first-in-human (FIH) study (NCT02361723).

Methods: Chinese patients with advanced non-mucinous high-grade ovarian cancer (HGOC) or triple-negative breast cancer (TNBC) whose disease either progressed despite standard therapy, or for which there is no standard therapy were enrolled in the dose-escalation (DE) portion of a phase 1/2 study (NCT03333915). The primary endpoint was safety/tolerability; secondary objectives were pharmacokinetics and antitumor activity. BRCA1/2 mutation status was retrospectively evaluated.

Results: Nine HGOC and six TNBC patients (N = 15; n = 4, 20 mg; n = 4, 40 mg; n = 7, 60 mg) were enrolled; as of 30 September 2019, one HGOC patient remained on treatment. Seven patients (n = 5, HGOC; n = 2, TNBC) had germline BRCA1/2 mutation (gBRCAmut ); all HGOC patients were resistant/refractory to platinum. Asthenia and nausea (n = 12 each) were the most common treatment-related adverse events (TRAEs). Decreased hemoglobin was the most common grade 3 TRAE (n = 3); no grade ≥4 AEs were observed. No dose-limiting toxicities (DLTs) were reported. Pamiparib plasma exposure was similar to exposure observed in the FIH study after a single-dose administration, albeit slightly higher at steady state. Among 13 RECIST-evaluable patients, two with HGOC (gBRCAmut , n = 1) achieved a confirmed partial response and six with HGOC (gBRCAmut , n = 4) achieved stable disease; all TNBC RECIST-evaluable patients (n = 5) reported progressive disease.

Conclusions: Pamiparib was generally well tolerated in Chinese patients, with durable responses observed in patients with HGOC. Based on these results, pamiparib 60 mg BID was confirmed as the RP2D.

Keywords: BGB-290; PARP inhibitor; high-grade ovarian cancer; pamiparib; triple-negative breast cancer.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • China
  • Drug Dosage Calculations
  • Female
  • Fluorenes / administration & dosage*
  • Fluorenes / adverse effects
  • Fluorenes / pharmacokinetics
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage*
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacokinetics
  • Progression-Free Survival
  • Time Factors
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Fluorenes
  • Poly(ADP-ribose) Polymerase Inhibitors
  • pamiparib

Associated data