
Results of the investigator-initiated phase II NIR-B trial shed light on the clinical utility of niraparib for patients with BRCA-mutated unresectable or recurrent biliary tract cancer (BTC), pancreatic cancer, and other gastrointestinal (GI) cancers.
Dr. Yasuyuki Kawamoto and colleagues presented the results at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Previous research suggests that BRCA1/2 mutations exist in biliary tract, pancreatic, and other GI cancers. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that may be effective for patients with these BRCA-mutated diseases.
Researchers sampled a total of 61 patients from March 2021 to April 2023 who had unresectable, advanced, or recurrent BTC (cohort A; n=26), pancreatic cancer (cohort B; n=26), and other GI cancers (cohort C; n=9). Patients had BRCA1/2 mutations and adequate organ function, but their disease was refractory to previous treatments or such treatments were intolerable.
Patients with a body weight of at least 77 kg and a platelet count of at least 150,000/µL received 300 mg of niraparib orally (once daily) until disease progression or intolerable adverse events occurred. Those weighing less than 77 kg or having a platelet count of less than 150,000/µL received 200 mg of niraparib.
The primary endpoint of NIR-B was objective response rate (ORR) in each cohort, with a threshold response rate of 10% and an expected response rate of 35%. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety.
Dr. Kawamoto and colleagues found the ORR to be 15.4%, 15.4%, and 0% in cohorts A, B, and C, respectively. DCR was 57.7%, 53.8%, and 22.2% in cohorts A, B, and C, respectively. Median PFS was 2.7 months, 1.8 months, and 1.4 months, in cohorts A, B, and C respectively; and median OS was 7.8 months, 9.5 month, and 7.4 months in cohorts A, B, and C, respectively.
In addition, pretreatment circulating tumor DNA was collected and analyzed by Guardant360. Among the patients identified with BRCA mutations by Guardant360, ORR was 11.1%, 19%, and 0% in cohorts A, B, and C, respectively.
The most commonly noted treatment-related adverse events were thrombocytopenia (31.1%), anemia (27.9%), neutropenia (14.8%), nausea (36.1%), fatigue (29.5%), and anorexia (24.6%).
“Although niraparib had signs of clinical activity in pts with BRCA-mutated BTC and pancreatic cancer, the primary endpoint was not achieved statistically,” study authors concluded. “Alternative approaches, such as evaluation in biomarker-selected patients or in combination with other agents, may demonstrate greater clinical activity of niraparib in this setting.”