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HORIZON-CRC01 — Trastuzumab rezetecan (HER2 ADC), HER2+ RAS/RAF wild-type chemo-refractory advanced colorectal cancer, 3rd line

Abstract: 3505 · Session: Gastrointestinal Cancer—Colorectal and Anal · Presenter: Jin Li, MD (Shanghai GoBroad Cancer Hospital Affiliated to China Pharmaceutical University, Shanghai, China) · Embargo: per ASCO 2026 embargo policy

At a glance

  • Sponsor: Jiangsu Hengrui Pharmaceuticals (Hengrui Pharma)
  • PI / presenter: Jin Li, MD; co-lead Ying Yuan, MD (Second Affiliated Hospital, Zhejiang University School of Medicine)
  • NCT ID: not specified in available sources (phase 1 program: NCT04513223)
  • Phase: 3
  • Design: Multicenter, open-label, randomized 2:1; stratified by HER2 status and performance status
  • N: 130 (86 trastuzumab rezetecan vs 44 control)
  • Primary endpoint(s): Progression-free survival (PFS) by independent review committee
  • Comparator: Physician's choice — TAS-102, fruquintinib, or regorafenib
  • Indication: HER2-positive, RAS/RAF wild-type advanced/metastatic colorectal cancer, progression after second-line therapy
  • Line: 3rd line (chemo-refractory)

Headline result

In HER2-positive, RAS/RAF wild-type chemo-refractory advanced CRC, trastuzumab rezetecan 4.8 mg/kg IV q3w significantly improved median PFS to 5.5 vs 2.8 months versus physician's-choice standard of care (HR 0.33, p<0.0001). Confirmed ORR was 40.7% vs 4.5% (p<0.001). Median OS was not reached with an immature OS HR of 0.77 (p=0.2651). Grade ≥3 treatment-related adverse events were comparable between arms (48.8% vs 50%); two treatment-related deaths occurred in the trastuzumab rezetecan arm.

Mechanism / class

Trastuzumab rezetecan (SHR-A1811) is a next-generation HER2-directed antibody–drug conjugate pairing a trastuzumab-based anti-HER2 antibody with a cleavable linker and a topoisomerase I inhibitor payload. It received its first regulatory approval in China in 2025. The same agent is in development across HER2-altered tumors including HER2-mutant NSCLC (HORIZON-Lung) and HER2-expressing gastric/GEJ cancer.

Practice-changing?

Pending. The first randomized phase 3 of a HER2 ADC in chemo-refractory HER2+ mCRC, with a striking PFS HR (0.33) and a >9-fold ORR advantage, establishes trastuzumab rezetecan as a strong candidate for this biomarker-selected niche. OS remains immature, the comparator chemotherapies are low-efficacy controls, and the trial was conducted entirely in China — global regulatory and guideline adoption will depend on OS maturity and ex-China data.

  • Other ASCO 2026 trials: same-class HER2 ADC / HER2+ GI — see other Hengrui trastuzumab rezetecan presentations in ./ if added
  • AACR 2026: ../../aacr-2026/index.md

Sources

  • HMP Global Learning Network (Oncology): https://www.hmpgloballearningnetwork.com/site/onc/news/trastuzumab-rezetecan-shows-strong-clinical-promise-her2-positive-advanced-colorectal
  • Targeted Oncology: https://www.targetedonc.com/view/trastuzumab-rezetecan-shows-promise-in-her2-expressing-gi-cancers
  • Hengrui Pharma press release (PRNewswire): https://www.prnewswire.com/news-releases/hengrui-pharma-presents-more-than-90-oncology-studies-at-asco-2026-highlighting-progress-across-multiple-tumor-types-302786778.html