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Precem-TcT as a Potential Option for Heavily Pretreated mCRC
Aug 2, 2025, 02:33

Precem-TcT as a Potential Option for Heavily Pretreated mCRC

A new study in Nature Medicine highlights Precem‑TcT (precemtabart tocentecan), a next‑generation antibody–drug conjugate targeting CEACAM5, a marker found on most colorectal cancers. Engineered to deliver a powerful chemotherapy payload directly to tumor cells—and even nearby cancerous tissue—Precem‑TcT has shown manageable safety and encouraging early activity in patients whose disease no longer responds to standard treatments.

Researchers say these results position the drug as a promising contender in the fight against advanced colorectal cancer.

Nicholas Hornstein and Yan Leyfman have Featured the Precem‑TcT in metastatic colorectal cancer on Social Media.

Nicholas Hornstein, Assistant Professor at Northwell Health:

“CEA was discovered in 1965.

By the 1970s, CEACAM5 was recognized as a hallmark of colorectal cancer.
Yet in 2025, CRC still has no approved ADCs.
That may change.

First-in-human data for Precem-TcT (anti-CEACAM5 + exatecan) now in Nature Medicine

PROCEADE-CRC-01 dose escalation (N=40, irinotecan-refractory mCRC):

Efficacy:

  • ORR: 7.5% confirmed (15% incl. unconfirmed)
  •  mPFS: 6.7 mo at DL ≥2.4 mg/kg
  •  10% still on treatment at cutoff

Safety:

  •  DLTs: mainly hematologic at higher doses
  •  No ILD, no ocular toxicity
  •  MTD: 2.8 mg/kg Q3W

Takeaway:

  • CEACAM5 has been an elusive target for decades.
  • Precem-TcT might finally make it actionable.
  • Early data suggest a foothold in 3L+ mCRC—where options are few and outcomes poor.
  • One to watch.

Fantastic to see my fellowship mentors continually push forward in a disease that needs better treatments.”

Yan Leyfman, Co-Founder and Executive Director of MedNews Week:

“New Hope in mCRC:

At PROCEADECRC01 Phase 1 trial, Precem-TcT (anti-CEACAM5 ADC with exatecan payload) shows promising activity in irinotecan-refractory metastatic colorectal cancer.

Key Highlights:

  • Targets CEACAM5, overexpressed in CRC
  • Confirmed PRs in 7.5% (15% unconfirmed); all at ≥2.4 mg/kg
  • Median PFS: 6.7 months at ≥2.4 mg/kg
  • Favorable safety profile: No ILD or ocular toxicity
  • Stable linker–payload confirmed by PK data
  • Ongoing dose optimization at 2.4 & 2.8 mg/kg Q3W

Early signals support Precem-TcT as a potential option for heavily pretreated mCRC.

Title: Precemtabart tocentecan, an anti-CEACAM5 antibody–drug conjugate, in metastatic colorectal cancer: a phase 1 trial

Authors: Scott Kopetz, Valentina Boni, Ken Kato, Kanwal P. S. Raghav, Maria Vieito, Athanasios Pallis, Christina Habermehl, Abdul Siddiqui, Perrine Courlet, Willem Sloot, Sabine Raab-Westphal, Felix Hart, Ildefonso Rodriguez-Rivera

Read the Full Article on Nature Medicine

Precem-TcT as a Potential Option for Heavily Pretreated mCRC

More posts featuring Nicholas Hornstein and Yan Leyfman.