Abstract 1684TiP
Background
PARP inhibitors are active in tumors with defect in homologous DNA repair by a mechanism known as synthetic lethality defined as defects in two or more separate proteins/pathways that induce cell death only when combined. Most studies of PARP inhibitors in pancreatic cancer have shown response rates of 20 to 25% in BRCA1/2 mutation carriers previously exposed to cytotoxic chemotherapy. Since mechanisms of resistance to platinum-based chemotherapy share some similarities with the mechanisms of resistance to PARP inhibitors, we hypothesize that PARP inhibitors may be significantly more active when used in chemotherapy-naïve patients and could represent a chemotherapy-free alternative for pancreatic cancers bearing defects in homologous recombination.
Trial design
This investigator initiated, multicentric, single arm, open-label, phase II aims to assess niraparib in chemotherapy-naïve biomarker-selected pancreatic cancer pts. Only pts with mutation and/or rearrangement, detected locally on tumor or liquid biopsy, leading to inactivation in at least one of the following genes BARD1, BRCA1, BRCA2, BRIP1, FANCA, FANCD2, FANCL, MRE11, NBN, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L are eligible. Included pts are treated with niraparib (300mg/d, orally) until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, pt or investigator decision. Primary endpoint is objective response rate after 16 weeks of treatment according to RECIST V1.1 (ORR16W). Secondary endpoints include duration of response, disease control rate, progression free survival, overall survival and safety. Using a Fleming-A’Hern single stage design with a target ORR16w of 60% and an inefficacy bound of 30% (α=5% one sided and 90% power) a total of 25 evaluable pts are required. If at least 16 successes (CR or PR at 16 weeks) are observed, niraparib will deserve further investigation. Correlative studies include documentation of HR alteration at time of progression on optional de novo tumor biopsy as well as assessment of predictive value for niraparib resistance of existing or new variants using liquid biopsies. To date, 4 French hospitals are participating.
Clinical trial identification
NCT05442749.
Editorial acknowledgement
Legal entity responsible for the study
Léon Bérard Center.
Funding
GSK.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1664P - Italian Association for Medical Oncology (AIOM) guideline application in real-world: Multi-institutional based survey of adjuvant and first-line pancreatic ductal adenocarcinoma treatment in Italy (GARIBALDI) - survival analyses in the metastatic cohort
Presenter: Michele Reni
Session: Poster session 22
1665P - Prognostic impact of diabetes and antidiabetic medication in pancreatic cancer patients
Presenter: Alexander Friedrich
Session: Poster session 22
1667P - Clinical and molecular features of young onset pancreatic adenocarcinoma
Presenter: Maxime Remond
Session: Poster session 22
1668P - Prevalence and management of pancreatic ductal adenocarcinoma (PDAC) over a decade in France: A population-based study
Presenter: Léo Mas
Session: Poster session 22
1670P - Tumoral and non-tumoral thrombosis associated with pancreatic ductal adenocarcinoma (PDAC): Survival impact, assessment of predictive scales and rethrombosis
Presenter: Alejandra Cardozo
Session: Poster session 22
1671P - Treatment patterns and efficacy in patients (pt) with pancreatic cancer (PC) from the Spanish RETUD registry
Presenter: Teresa Macarulla
Session: Poster session 22
1673P - Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: The champ study
Presenter: Sofie Olsson Hau
Session: Poster session 22
1674P - VILP registry of patients with metastatic pancreatic cancer treated with pegylated liposomal irinotecan plus 5-fluoroucil and leucovorin in the Czech Republic
Presenter: Stanislav Batko
Session: Poster session 22
1675P - Diagnostic performance of blood-based DNA methylation assay using epigenetic-specific peptide nucleic acid in pancreatic adenocarcinoma
Presenter: Hongsik Kim
Session: Poster session 22