precemtabart tocentecan (M9140) / EMD Serono - LARVOL DELTA

Precemtabart tocentecan (Precem-TcT, M9140): Results from the phase I PROCEADE-CRC-01 dose optimization and a post-hoc analysis in Asian patients (ESMO Asia 2025) - P1, P1/2 | "Background: Precem-TcT, an anti-CEACAM5 ADC with an exatecan payload (TOP1 inhibitor), showed manageable safety and encouraging early efficacy in patients (pts) with 3L+ irinotecan-refractory metastatic CRC (mCRC) in PROCEADE-CRC-01 (NCT05464030; dose escalation). In the dose optimization part, pts received Precem-TcT 2.8 mg/kg Q3W (Arm [A]1) or 2.4 mg/kg Q3W (A2; 1:1 randomization). Overall, 60 pts were treated (A1, n=29; A2, n=31), with 25 still on treatment at data cutoff (Mar 2025). Efficacy of Precem-TcT in 3L+ mCRC (especially at 2.8 mg/kg Q3W), including in Asian pts, compares favorably with available therapies. Safety profiles were manageable and comparable between DLs. PK was similar between overall and Asian populations."

Clinical • P1 data • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor • CEACAM5 • TOP1

Precemtabart tocentecan (Precem-TcT, M9140) in patients with mCRC: Efficacy and safety data at the recommended development dose in the PROCEADE-CRC-01 study. (ASCO-GI 2026) - P1 | "Funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) Clinical Trial Registration Number: NCT05464030 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Colorectal Cancer • Gastrointestinal Cancer

Precemtabart tocentecan (M9140), an anti-CEACAM5 ADC with exatecan payload, in patients with metastatic colorectal cancer: Updated clinical data from the phase I PROCEADE-CRC-01 study (ESMO 2025) - P1, P1/2 | "Background Precem-TcT, the first anti-CEACAM5 ADC with an exatecan payload (Top1 inhibitor), showed a manageable safety profile and promising clinical activity during dose escalation of the Ph1 PROCEADE-CRC-01 study (NCT05464030) in pts with 3L+ irinotecan-pretreated mCRC. The encouraging efficacy, with an unconfirmed ORR of 31% at 2.8 mg/kg Q3W, and predictable, manageable safety profile support further clinical development of precem-TcT (recommended dose: 2.8 mg/kg Q3W) in mCRC and other CEACAM5-expressing solid tumors (PROCEADE-PanTumor; NCT06710132). More updated data, including OS, will be presented at ESMO."

Clinical data • Metastases • P1 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CEACAM5 • KRAS • NRAS • TOP1

Precemtabart tocentecan, an anti-CEACAM5 antibody-drug conjugate, in metastatic colorectal cancer: a phase 1 trial. (PubMed, Nat Med) - P1 | "Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody-drug conjugate with the topoisomerase 1 inhibitor exatecan as payload...In the dose-escalation stage of the phase 1 trial of Precem-TcT (PROCEADE-CRC-01), 40 heavily pretreated patients with irinotecan-refractory metastatic CRC received Precem-TcT every 3 weeks across seven dose levels (DLs, 0.6-3.2 mg kg-1)...The dose-optimization part at the RDEs of 2.4 mg kg-1 and 2.8 mg kg-1 (both every 3 weeks) in PROCEADE-CRC-01 is ongoing. ClinicalTrials.gov identifier: NCT05464030 ."

Journal • P1 data • Colorectal Cancer • Genetic Disorders • Hematological Disorders • Interstitial Lung Disease • Obesity • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • CEACAM5

Precemtabart tocentecan, an anti-CEACAM5 antibody–drug conjugate, in metastatic colorectal cancer: a phase 1 trial (Nature) - P1 | N=200 | PROCEADE-CRC-01 (NCT05464030) | Sponsor: EMD Serono Research & Development Institute, Inc. | "At the planned, end-of-dose-escalation analysis with extended follow-up (cutoff: 1 August 2024), seven patients had experienced DLTs, primarily hematologic events at 3.0 mg kg−1 and 3.2 mg kg−1...The maximum tolerated dose was determined to be 2.8 mg kg−1 every 3 weeks. Total and conjugated antibody pharmacokinetic profiles largely overlapped, indicating stability of the linker–payload (β-glucuronide–exatecan) in circulation. After a median treatment of 19.1 weeks (range: 1.7–48.3), three of 40 patients (7.5%) had confirmed partial responses (15.0% (6/40) unconfirmed)....Precem-TcT demonstrated potent inhibition of cancer cell growth in cell lines expressing the CEACAM5 protein, specifically SK-CO-1 and MKN-45, with 50% inhibitory concentration (IC50) values of 0.09 nM and 0.63 nM, respectively."

P1 data • Preclinical • Colorectal Cancer

Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01) (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • MSI

Anti-CEACAM5 ADC M9140 in Chinese Participants With Solid Tumors (PROCEADE-CRC-02) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Trial completion date: Aug 2026 ➔ May 2026

Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor) (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2029 ➔ Jan 2028 | Trial primary completion date: Jan 2029 ➔ Jan 2028

Pan tumor • Trial completion date • Trial primary completion date • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

PROCEADE PanTumor: A phase 1b/2, multicenter study of precemtabart tocentecan (M9140), an anti-CEACAM5 antibody-drug conjugate (ADC) with exatecan payload, in patients with advanced solid tumors. (ASCO 2025) - P1/2 | "Originally presented at AACR 2025. Reprinted with permission."

Clinical • Metastases • P1/2 data • Pan tumor • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CEACAM5 • EGFR • HER-2

Precemtabart tocentecan (M9140), an anti-CEACAM5 ADC with exatecan payload, in patients with metastatic colorectal cancer (mCRC): Results from the dose optimization of the phase 1 PROCEADE CRC-01 study. (ASCO 2025) - P1, P1/2 | " This global Phase 1 study in 3L adult patients with locally advanced/mCRC (ECOG PS ≤1; previous irinotecan therapy) evaluates clinical activity, safety, and tolerability of precemtabart tocentecan... These preliminary results corroborate the encouraging efficacy and safety data from the dose escalation part of the PROCEADE CRC-01 study, with no new relevant safety findings. ORR was higher at 2.8 mg/kg, with similar tolerability at both doses. The ORR of 24.1% (13.8% confirmed) at 2.8 mg/kg compares favorably with current monotherapy SoCs (ORRs 1-2%) and recent phase 3 data with trifluridine–tipiracil + bevacizumab (ORR 6.1%) in 3L+ mCRC."

Clinical • Metastases • P1 data • Anemia • Colorectal Cancer • Febrile Neutropenia • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CEACAM5

ASCO25: Merck KGaA’s ADC shows safety and tolerability in colorectal cancer trial (Clinical Trials Arena) - P1 | N=200| PROCEADE-CRC-01 (NCT05464030) | "As of the March 25 data cut-off, 42% of patients enrolled in the dose expansion phase of the Phase Ib study remain on treatment, with three patients having continued treatment for nine months. The median duration of response (DoR) is 23.3 weeks, with nearly 60% of patients having had six cycles of treatment. The median progression free survival (PFS) is 6.9 months, and there was a 72% disease control rate at week 12. In the study, the most common adverse events (AEs) were anaemia and neutropenia, with no cases of interstitial lung disease (ILD) or ocular toxicity noted in the study. There were no discontinuations or treatment related deaths."

P1 data • Colorectal Cancer

Merck Showcases Innovation in Advanced Cancers and Rare Tumors at ASCO 2025 (Businesswire) - "Merck...announced the presentation of new oncology data across more than 12 tumor types at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31 to June 4 in Chicago. The presentations include the Phase 3 MANEUVER data for potentially best-in-class pimicotinib in the treatment of the rare tumor TGCT, as well as data from both company- and investigator-sponsored studies highlighting the company’s focus on advancing differentiated molecules to tackle some of the most challenging cancers."

Clinical data • P3 data • Bladder Cancer • Colorectal Cancer • Merkel Cell Carcinoma • Tenosynovial Giant Cell Tumor • Urothelial Cancer

PROCEADE PanTumor: A Phase 1b/2, multicenter study of precemtabart tocentecan (M9140), an anti-CEACAM5 antibody-drug conjugate (ADC) with exatecan payload, in patients with advanced solid tumors (AACR 2025) - P1/2 | "The study is planned to be initiated at multiple sites globally, with an estimated enrollment of 250 patients. Clinical trial information: NCT06710132."

Clinical • Metastases • P1/2 data • Pan tumor • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CEACAM5 • EGFR • HER-2

M9140: Data from dose expansion part of P1b PROCEADE-CRC-01 trial (NCT05464030) for colorectal cancer in Q2 2025 (EMD Serono) - Q4 2024 Results

P1 data • Colorectal Cancer • Oncology • Solid Tumor

Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor) (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastric Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Anti-CEACAM5 ADC M9140 in Chinese Participants With Solid Tumors (PROCEADE-CRC-02) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor

Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor) (clinicaltrials.gov) - P1/2 | N=250 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

Metastases • New P1/2 trial • Pan tumor • Gastric Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

M9140, an anti-CEACAM5 antibody drug conjugate (ADC), in patients with metastatic colorectal cancer (mCRC): Updated results from a phase I trial (ESMO 2024) - P1 | "With continued follow-up, M9140 continues to exhibit a manageable and predictable safety profile. Encouraging antitumor activity was observed at DLs ≥2.4 mg/kg. DLs 2.4 and 2.8 mg/kg, identified as the recommended doses for expansion, are currently being evaluated in the randomized dose optimization part of the study."

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • CEACAM5 • KRAS • NRAS

PROCEADE-CRC-01: an anti-CEACAM5 ADC for metastatic colorectal cancer (YouTube) - "Scott Kopetz, MD...presents findings from the Phase I PROCEADE-CRC-01 trial (NCT05464030) of M9140, an anti-CEACAM5 antibody-drug conjugate (ADC), in metastatic colorectal cancer. Designed with an exatecan payload, this ADC showed promising results due to its stability and specific targeting of CEACAM5-expressing tumors."

Interview • Video

OmniAb Reports Second Quarter 2024 Financial Results and Business Highlights (Businesswire) - "M9140: (i) At the American Association for Cancer Research Annual Meeting, Merck KGaA presented data on M9140, a novel antibody-drug conjugate with topoisomerase 1 inhibitor payload targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expressing tumors.​ M9140 demonstrated high potency, strong antitumor activity and bystander effect in preclinical models; (ii) A first-in-human Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary clinical activity of M9140 in patients with advanced solid tumors is ongoing."

Preclinical • Trial status • Solid Tumor

Merck’s Innovative Oncology Pipeline of DNA Damage Response Inhibitors and Antibody-Drug Conjugates Poised to Advance Cancer Treatment (Businesswire) - "Merck...shared updates on the company’s oncology pipeline and focused approach to the research and development of potential new medicines designed to improve the futures of people with cancer...This year, the company plans to open multiple new Phase Ib and II clinical studies for tuvusertib and M9466...updates were shared at the company’s Oncology R&D Update Call...A basket trial planned to launch in early 2025 will further explore M9140 monotherapy in tumors with high CEACAM5 expression, with the potential for further exploration in various combinations...M3554 is the next ADC based on the company’s platform, linking an exatecan payload with an anti-GD2 antibody. This potentially first-in-class ADC will enter its first-in-human study later in 2024."

New P1 trial • New P2 trial • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Osteosarcoma • Ovarian Cancer • Prostate Cancer • Sarcoma • Solid Tumor

First-in-human trial of M9140, an anti-CEACAM5 antibody drug conjugate (ADC) with exatecan payload, in patients (pts) with metastatic colorectal cancer (mCRC). (ASCO 2024) - P1 | "Most pts were heavily pretreated (80% had ≥3 lines of prior treatment; 100% received irinotecan). M9140 demonstrated encouraging activity in heavily pretreated pts with advanced CRC, with a manageable and predictable safety profile. Contrary to approved ADCs with Top1i payloads, no ILD or ocular toxicities were observed. Evaluation of M9140 in mCRC continues in the dose expansion part of this study."

Clinical • Metastases • P1 data • Anemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Infectious Disease • Interstitial Lung Disease • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor • Thrombocytopenia • CEACAM5

Merck to Showcase Advances in the Science of Cancer With New Data Presented at ASCO 2024 (Businesswire) - P1 | N=180 | NCT05464030 | Sponsor: EMD Serono Research & Development Institute, Inc. | "Merck...announced new research from the company’s diverse oncology portfolio will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31 to June 4, Chicago. Data from company- and investigator-sponsored studies include 31 accepted abstracts across more than 10 tumor types, including seven oral presentations, highlighting the company’s innovative oncology pipeline encompassing potential first-in-class approaches designed to hit cancer at its core....Data from 40 patients treated across seven dose levels in Part 1A of the study showed encouraging clinical activity and a manageable and predictable safety profile in this population. The randomized dose-expansion part of the study is ongoing."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: May 2025 ➔ Feb 2026 | Trial primary completion date: Apr 2024 ➔ Feb 2026

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=31 ➔ 180 | Trial completion date: Nov 2023 ➔ May 2025 | Trial primary completion date: Nov 2023 ➔ Apr 2024

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI