Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101676423 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-3635 (Electronic) Linking ISSN: 20593635 NLM ISO Abbreviation: Signal Transduct Target Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Publishing Group, [2016]-
    • Subject Terms:
      Capecitabine*/administration & dosage ; Colorectal Neoplasms*/drug therapy ; Colorectal Neoplasms*/pathology ; Colorectal Neoplasms*/genetics ; Bevacizumab*/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols*/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols*/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols*/adverse effects ; Neoplasm Metastasis*; Humans ; Female ; Male ; Middle Aged ; Aged ; Adult ; Oxaloacetates ; Fluorouracil/administration & dosage ; Oxaliplatin/administration & dosage ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/administration & dosage ; Antibodies, Monoclonal ; Recombinant Fusion Proteins
    • Abstract:
      This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.5 mg/kg), and oxaliplatin (130 mg/m 2 ) intravenously on day 1, along with oral capecitabine (1 g/m 2 twice daily) on days 1-14 of 21-day cycles. Up to eight induction cycles were administered, followed by maintenance therapy for responders or those with stable disease. The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1. The combination achieved an ORR of 59.7% and a disease control rate (DCR) of 83.9%. Median progression-free survival (PFS) was 10.3 months (95% CI: 8.3-13.7), with 6- and 12-month PFS rates of 77.2% and 41.3%, respectively. The estimated 12-month overall survival (OS) rate was 67.7%. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 59.7% of patients, with anemia and neutropenia (8.1% each) being the most common. Retrospective DNA sequencing revealed that high tumor mutational burden, neo-antigens, and SBS15 enrichment correlated with better responses. Elevated baseline lactate dehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safety profile and potent antitumor activity in unresectable mCRC.
      Competing Interests: Competing interests: W.D., Y.J., and C.H. are employees of Jiangsu Hengrui Pharmaceuticals. The remaining authors declare no conflicts of interest.
      (© 2024. The Author(s).)
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    • Grant Information:
      82321003, 82173128, 81930065 National Natural Science Foundation of China (National Science Foundation of China); 82073377 National Natural Science Foundation of China (National Science Foundation of China); 2021A1515012439 Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)
    • Accession Number:
      6804DJ8Z9U (Capecitabine)
      2S9ZZM9Q9V (Bevacizumab)
      0 (Oxaloacetates)
      U3P01618RT (Fluorouracil)
      04ZR38536J (Oxaliplatin)
      0W860991D6 (Deoxycytidine)
      0 (SHR-1701)
      0 (Antibodies, Monoclonal)
      0 (Recombinant Fusion Proteins)
    • Subject Terms:
      XELOX
    • Publication Date:
      Date Created: 20241215 Date Completed: 20241215 Latest Revision: 20250104
    • Publication Date:
      20250114
    • Accession Number:
      PMC11647033
    • Accession Number:
      10.1038/s41392-024-02063-0
    • Accession Number:
      39676137