Precemtabart tocentecan

Shows activity

Also known as:

M9140 Precem-TcT

Cancer types include:

colon cancer non-small cell lung cancer pancreas cancer rectal cancer small cell lung cancer

TrialFetch AI Analysis

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Overview

M9140 (now named precemtabart tocentecan, “Precem‑TcT”) is an investigational anti‑CEACAM5 antibody–drug conjugate (ADC) developed by Merck KGaA/EMD Serono. It is being tested primarily in metastatic colorectal cancer (mCRC) and, via a master protocol (PROCEADE PanTumor), in other CEACAM5‑expressing solid tumors (gastric cancer, NSCLC, pancreatic cancer). A first‑in‑human Phase 1 trial in mCRC (PROCEADE‑CRC‑01; NCT05464030) has reported dose‑escalation results, and subsequent Phase 1b/2 studies are enrolling. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Target: Carcinoembryonic antigen–related cell adhesion molecule 5 (CEACAM5), overexpressed in many adenocarcinomas (notably CRC) and limited in normal adult tissues. (ascopubs.org)
Construct: A human anti‑CEACAM5 monoclonal antibody conjugated via a hydrophilic β‑glucuronide linker to the topoisomerase‑I inhibitor exatecan; drug‑to‑antibody ratio (DAR) = 8. The linker–payload is designed to be stable in circulation and release membrane‑permeable exatecan intracellularly, enabling a bystander effect. (ascopubs.org)

Clinical development and trial status

First‑in‑human Phase 1 (PROCEADE‑CRC‑01; NCT05464030): dose escalation complete; randomized dose optimization/expansion ongoing. Recommended doses for expansion (RDEs): 2.4 and 2.8 mg/kg IV every 3 weeks; maximum tolerated dose (MTD): 2.8 mg/kg Q3W. (pubmed.ncbi.nlm.nih.gov)
PROCEADE PanTumor (Phase 1b/2): master protocol evaluating monotherapy and combinations in advanced gastric cancer, NSCLC, and pancreatic cancer; multiple sites active and enrolling. (aacrjournals.org)

Efficacy

Dose‑escalation results in heavily pretreated, irinotecan‑refractory mCRC:

Objective responses: In the Nature Medicine report (cutoff 1 Aug 2024), confirmed partial responses (PR) in 3/40 (7.5%); unconfirmed PR in 6/40 (15%); all responses occurred at ≥2.4 mg/kg. Median PFS was 5.9 months overall and 6.7 months at doses ≥2.4 mg/kg. (pubmed.ncbi.nlm.nih.gov)
ASCO 2024 and institutional summaries reported PRs in 10% and stable disease in 42.5% (preliminary median PFS 6.7 months), consistent with the higher‑dose subset. (mdanderson.org)
Conference updates (ESMO 2024) reiterated encouraging antitumor activity at ≥2.4 mg/kg and ongoing randomized dose optimization. (oncologypro.esmo.org)

Safety

In the Phase 1 dose‑escalation (cutoff 1 Aug 2024), dose‑limiting toxicities were primarily hematologic at 3.0–3.2 mg/kg. No interstitial lung disease (ILD) or ocular toxicities were observed; one treatment‑related death occurred in a patient with multiple comorbidities and grade 3 obesity. (pubmed.ncbi.nlm.nih.gov)
Earlier ASCO 2024 data also noted a manageable, predictable safety profile without ILD or ocular events, contrasting with some other Top1i‑ADC experiences. (ascopubs.org)
Nonclinical safety studies in cynomolgus monkeys showed dose‑dependent gastrointestinal and hematolymphoid effects consistent with exatecan, and no ILD signal, supporting a low ILD risk hypothesis for M9140’s linker‑payload design. (pubmed.ncbi.nlm.nih.gov)

Active trials using Precemtabart tocentecan

Found 3 active trials using this drug:

A Randomized, Open Label, 3-arm Phase 3 Study of Precemtabart Tocentecan With or Without Bevacizumab Compared to Trifluridine/Tipiracil Plus Bevacizumab in Participants With Previously Treated Metastatic Colorectal Cancer (PROCEADE-CRC-03)

Sponsor: EMD Serono Research & Development Institute, Inc. (industry) Phase: 3 Start date: May 6, 2026

TrialFetch AI summary: Adults with ECOG 0–1 metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab, with no more than 2 prior metastatic regimens, are randomized to later-line therapy. The study compares precemtabart tocentecan, a CEACAM5-directed antibody–drug conjugate with an exatecan topoisomerase I inhibitor payload, with or without bevacizumab versus trifluridine/tipiracil plus bevacizumab.

ClinicalTrials.gov ID: NCT07549412

PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Solid Tumors (Master Protocol)

Sponsor: EMD Serono Research & Development Institute, Inc. (industry) Phase: 1/2 Start date: Jan. 29, 2025

TrialFetch AI summary: Eligible patients are adults with advanced or metastatic gastric/GEJ adenocarcinoma, NSCLC, or pancreatic ductal adenocarcinoma expressing CEACAM5, who have progressed after 1–3 prior systemic therapies. The trial investigates M9140, an antibody-drug conjugate targeting CEACAM5 and delivering a topoisomerase I inhibitor payload, as monotherapy in these populations.

ClinicalTrials.gov ID: NCT06710132

A Phase I, Multicenter, Open-Label First in Human Study of Anti-CEACAM5 Antibody Drug Conjugate M9140 in Participants With Advanced Solid Tumors (PROCEADE-CRC-01)

Sponsor: EMD Serono Research & Development Institute, Inc. (industry) Phase: 1 Start date: Aug. 4, 2022

TrialFetch AI summary: This trial enrolls adults with refractory or metastatic colorectal cancer who have progressed after standard therapies, including immunotherapy for MSI-high tumors. Patients receive M9140, an antibody-drug conjugate targeting CEACAM5 and delivering a topoisomerase 1 inhibitor (exatecan), either alone or in combination with metastatic colorectal cancer standard regimens (bevacizumab, capecitabine, or 5-FU/folinic acid).

ClinicalTrials.gov ID: NCT05464030