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Pamiparib dose escalation in Chinese patients with non‐mucinous high‐grade ovarian cancer or advanced triple‐negative breast cancer
- Source :
- Cancer Medicine
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
Abstract
- 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 (gBRCA mut); 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 (gBRCA mut, n = 1) achieved a confirmed partial response and six with HGOC (gBRCA mut, 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.<br />Pamiparib (an investigational PARP1/2 inhibitor) 60 mg BID was confirmed as the recommended phase 2 dose in Chinese patients with advanced non‐mucinous high‐grade ovarian cancer (HGOC) or triple‐negative breast cancer whose disease progressed despite standard therapy, or for which there is no standard therapy. Pamiparib 60 mg BID was generally well tolerated with asthenia and nausea being the most commonly reported treatment‐related adverse events. Clinical durable responses were observed among patients with HGOC, all of whom were resistant/refractory to platinum chemotherapy and most with gBRCA mut.
- Subjects :
- 0301 basic medicine
Adult
Cancer Research
medicine.medical_specialty
China
Time Factors
Nausea
Triple Negative Breast Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Breast cancer
Internal medicine
medicine
Clinical endpoint
Humans
Radiology, Nuclear Medicine and imaging
Drug Dosage Calculations
Adverse effect
Triple-negative breast cancer
Original Research
Aged
BRCA2 Protein
Ovarian Neoplasms
Fluorenes
business.industry
BRCA1 Protein
BGB‐290
pamiparib
Clinical Cancer Research
Middle Aged
medicine.disease
Progression-Free Survival
030104 developmental biology
PARP inhibitor
triple‐negative breast cancer
Oncology
Tolerability
030220 oncology & carcinogenesis
Mutation
Female
medicine.symptom
high‐grade ovarian cancer
Neoplasm Grading
business
Ovarian cancer
Progressive disease
Subjects
Details
- Language :
- English
- ISSN :
- 20457634
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cancer Medicine
- Accession number :
- edsair.doi.dedup.....4fec3ad2b8afbc263ae99180ecc7ba83