Detalle Publicación

Motixafortide and pembrolizumab combined to nanoliposomal irinotecan, fluorouracil, and folinic acid in metastatic pancreatic cancer: the COMBAT/KEYNOTE-202 trial

Autores: Bockorny, B. ; Macarulla, T.; Semenisty, V.; Borazanci, E.; Feliu, J.; Ponz Sarvisé, Mariano; Gutiérrez Abad, D.; Oberstein, P.; Alistar, A.; Muñoz, A.; Geva, R.; Guillen-Ponce, C.; Salgado Fernández, M.; Peled, A.; Chaney, M.; Gliko-Kabir, I.; Shemesh-Darvish, L.; Ickowicz, D.; Sorani, E.; Kadosh, S.; Vainstein-Haras, A.; Hidalgo, M. (Autor de correspondencia)
Título de la revista: CLINICAL CANCER RESEARCH
ISSN: 1078-0432
Volumen: 27
Número: 18
Páginas: 5020 - 5027
Fecha de publicación: 2021
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study evaluates dual blockade of CXCR4 and PD1 with chemotherapy in PDAC. Patients and Methods: Multicenter, single-arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined with chemotherapy in patients with de novo metastatic PDAC and disease progression on front-line gemcitabine-based therapy (NCT02826486). Subjects received a priming phase of motixafortide daily on days 1-5, followed by repeated cycles of motixafortide twice a week; pembrolizumab every 3 weeks; and nanoliposomal irinotecan, fluorouracil, and leucovorin every 2 weeks (NAPOLI-1 regimen). The primary objective was objective response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), safety, and tolerability. Results: A total of 43 patients were enrolled. The ORR according to RECISTv1.1 was 21.1% with confirmed ORR of 13.2%. The DCR was 63.2% with median duration of clinical benefit of 5.7 months. In the intention-to-treat population, median PFS was 3.8 months and median OS was 6.6 months. The triple combination was safe and well tolerated, with toxicity comparable with the NAPOLI-1 regimen. Notably, the incidence of grade 3 or higher neutropenia and infection was 7%, lower than expected for this chemotherapy regimen. Conclusions: Triple combination of motixafortide, pembrolizumab, and chemotherapy was safe and well tolerated, and showed signs of efficacy in a population with poor prognosis and aggressive disease.