Motixafortide and Pembrolizumab Combined to Nanoliposomal Irinotecan, Fluorouracil, and Folinic Acid in Metastatic Pancreatic Cancer: The COMBAT/KEYNOTE-202 Trial

• Published in: Clinical cancer research Vol. 27; no. 18; pp. 5020 - 5027
• Main Authors: Bockorny, Bruno, Macarulla, Teresa, Semenisty, Valerya, Borazanci, Erkut, Feliu, Jaime, Ponz-Sarvise, Mariano, Abad, David Gutierrez, Oberstein, Paul, Alistar, Angela, Muñoz, Andres, Geva, Ravit, Guillén-Ponce, Carmen, Fernandez, Mercedes Salgado, Peled, Amnon, Chaney, Marya, Gliko-Kabir, Irit, Shemesh-Darvish, Liron, Ickowicz, Debby, Sorani, Ella, Kadosh, Shaul, Vainstein-Haras, Abi, Hidalgo, Manuel
• Format: Journal Article
• Language: English
• Published: United States 15.09.2021
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - secondary; Female; Fluorouracil - administration & dosage; Humans; Irinotecan - administration & dosage; Leucovorin - administration & dosage; Liposomes; Male; Middle Aged; Nanoparticles; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Peptides - administration & dosage
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-21-0929

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. Multicenter, single-arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined with chemotherapy in patients with 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. 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. 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.