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Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study

 Choong-Kun Lee  ;  Jii Bum Lee  ;  Se Jung Park  ;  Jingmin Che  ;  Woo Sun Kwon  ;  Hyo Song Kim  ;  Minkyu Jung  ;  Seulkee Lee  ;  Sook Ryun Park  ;  Dong-Hoe Koo  ;  Hyun Woo Lee  ;  Woo Kyun Bae  ;  Hei-Cheul Jeung  ;  In Gyu Hwang  ;  Hyunki Kim  ;  Chung Mo Nam  ;  Hyun Cheol Chung  ;  Sun Young Rha 
 GASTRIC CANCER, Vol.27(1) : 118-130, 2024-01 
Journal Title
Issue Date
Antineoplastic Combined Chemotherapy Protocols ; Biomarkers ; Epstein-Barr Virus Infections* ; Herpesvirus 4, Human ; Humans ; Immunotherapy ; Nivolumab / adverse effects ; Nivolumab / therapeutic use ; Paclitaxel ; Stomach Neoplasms*
Advanced gastric cancer ; Biomarker enriched ; Immune checkpoint inhibitors ; Nivolumab ; Paclitaxel
Background: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC).

Methods: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m2 or dose level 2, 80 mg/m2) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis.

Results: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival.

Conclusions: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Woo Sun(권우선) ORCID logo https://orcid.org/0000-0003-0268-5624
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Nam, Chung Mo(남정모) ORCID logo https://orcid.org/0000-0003-0985-0928
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Lee, Jii Bum(이기쁨) ORCID logo https://orcid.org/0000-0001-5608-3157
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
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