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

Bruno Bockorny, Teresa Macarulla, Valerya Semenisty, Erkut Borazanci, Jaime Feliu, Mariano Ponz-Sarvise, David Gutierrez Abad, Paul Oberstein, Angela Alistar, Andres Muñoz, Ravit Geva, Carmen Guillen-Ponce, Mercedes Salgado Fernandez, Amnon Peled, Marya Chaney, Irit Gliko-Kabir, Liron Shemesh-Darvish, Debby Ickowicz, Ella Sorani, Shaul KadoshAbi Vainstein-Haras, Manuel Hidalgo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)5020-5027
Number of pages8
JournalClinical Cancer Research
Volume27
Issue number18
DOIs
StatePublished - 15 Sep 2021
Externally publishedYes

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