The efficacy and safety of suvemcitug, envafolimab, and FOLFIRI in microsatellite-stable or mismatch repair-proficient colorectal cancer: preliminary results of a phase 2 study

Int J Colorectal Dis. 2025 Jan 21;40(1):20. doi: 10.1007/s00384-025-04806-z.

Abstract

Purpose: This phase II study is designed to evaluate the combination therapy involving suvemcitug and envafolimab with FOLFIRI in microsatellite-stable or mismatch repair-proficient (MSS/pMMR) colorectal cancer (CRC) in the second-line treatment setting.

Methods: This study is a non-randomized, open-label prospective study comprising multiple cohorts (NCT05148195). Here, we only report the data from the CRC cohort. Participants received envafolimab, suvemcitug, and FOLFIRI until disease progression, unacceptable toxicity, or voluntary withdrawal. The recommended dose (RD) and objective response rate (ORR) by investigator assessment were primary endpoints. Secondary endpoints comprised progression-free survival (PFS) and duration of response (DoR). Disease control rate (DCR), overall survival (OS), and safety were also analyzed.

Results: At the data cutoff, no dose-limiting toxicity event was observed in the safety run-in stage, and 2 mg/kg Q2W was declared as RD for suvemcitug combined with envafolimab and FORFIRI. Among 20 patients, 50.0% and 10.0% had been treated with prior antiangiogenic agents and anti-EGFR agents, respectively. ORR and DCR were 25.0% (95% CI 8.7-49.1%) and 90.0% (95% CI 68.3-98.8%), and DoR was 4.1 months (95% CI 3.02, NE). The median PFS and median OS were 5.6 months (95% CI 4.0-8.3) and not reached (95% CI 8.5, NE) by the time of study closure. Neutrophil count decreased, white blood cell count decreased, and hypertension were the most common grade ≥3 treatment-related adverse events (TRAE).

Conclusions: The safety profile was manageable and the preliminary anti-tumor efficacy was observed in patients with MSS/pMMR CRC in this study, who had failed prior to one line of therapy.

Keywords: Anti-tumor activities; Colorectal cancer; Envafolimab; MSS/pMMR; Suvemcitug.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • DNA Mismatch Repair*
  • Female
  • Fluorouracil* / adverse effects
  • Fluorouracil* / therapeutic use
  • Humans
  • Leucovorin* / adverse effects
  • Leucovorin* / therapeutic use
  • Male
  • Microsatellite Instability / drug effects
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Progression-Free Survival
  • Prospective Studies
  • Treatment Outcome

Substances

  • Leucovorin
  • Fluorouracil
  • Camptothecin
  • Antibodies, Monoclonal, Humanized

Supplementary concepts

  • IFL protocol