TY - JOUR
T1 - Motixafortide and pembrolizumab combined to nanoliposomal irinotecan, fluorouracil, and folinic acid in metastatic pancreatic cancer
T2 - The COMBAT/ KEYNOTE-202 trial
AU - Bockorny, Bruno
AU - Macarulla, Teresa
AU - Semenisty, Valerya
AU - Borazanci, Erkut
AU - Feliu, Jaime
AU - Ponz-Sarvise, Mariano
AU - Abad, David Gutierrez
AU - Oberstein, Paul
AU - Alistar, Angela
AU - Muñoz, Andres
AU - Geva, Ravit
AU - Guillen-Ponce, Carmen
AU - Fernandez, Mercedes Salgado
AU - Peled, Amnon
AU - Chaney, Marya
AU - Gliko-Kabir, Irit
AU - Shemesh-Darvish, Liron
AU - Ickowicz, Debby
AU - Sorani, Ella
AU - Kadosh, Shaul
AU - Vainstein-Haras, Abi
AU - Hidalgo, Manuel
N1 - Publisher Copyright:
2021 American Association for Cancer Research
PY - 2021/9/15
Y1 - 2021/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85115023729&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-0929
DO - 10.1158/1078-0432.CCR-21-0929
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C2 - 34253578
AN - SCOPUS:85115023729
SN - 1078-0432
VL - 27
SP - 5020
EP - 5027
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -