Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis

Cell Rep Med. 2021 Aug 27;2(9):100383. doi: 10.1016/j.xcrm.2021.100383. eCollection 2021 Sep 21.

Abstract

This is a phase Ib/II study of regorafenib plus toripalimab for colorectal cancer. The objective response rate (ORR) is 15.2% and the disease control rate is 36.4% in evaluable patients with recommended phase II dose (80 mg regorafenib plus toripalimab). The median progression-free survival (PFS) and the median overall survival are 2.1 months and 15.5 months, respectively. Patients with liver metastases have lower ORR than those without (8.7% versus 30.0%). All patients (3/3) with lung-only metastasis respond, whereas no patients (0/4) with liver-only metastasis respond. 94.9% and 38.5% of patients have grade 1 and grade 3 treatment-related adverse events, respectively. Gut microbiome analysis of the baseline fecal samples shows significantly increased relative abundance and positive detection rate of Fusobacterium in non-responders than responders. Patients with high-abundance Fusobacterium have shorter PFS than those with low abundance (median PFS = 2.0 versus 5.2 months; p = 0.002).

Keywords: colorectal cancer; immunotherapy; microbiome; programmed cell death protein 1; regorafenib; toripalimab.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / microbiology*
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • toripalimab