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)

The PROCEADE PanTumor study aims to investigate M9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and it is therefore designed as a matrix study. This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult participants with locally advanced/metastatic CEACAM5 expressing tumors. There will be 3 substudies under this Master Protocol that may be conducted in parallel.
* PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Gastric Cancer (Substudy GC);
* PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Non-Small Cell Lung Cancer (Substudy NSCLC);
* PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Pancreatic Cancer (Substudy PDAC).

Start Date29 Jan 2025

Sponsor / Collaborator

EMD Serono Research & Development Institute, Inc.

[+2]

NCT06806046

/ RecruitingPhase 1

A Phase 1, Open-label Study of AntiCEACAM5 AntibodyDrug Conjugate M9140 in Chinese Participants With Solid Tumors (PROCEADE-CRC-02)

The purpose of this study is to evaluate the safety and early clinical activity of M9140 in Chinese participants with locally advanced or metastatic colorectal cancer (CRC).

Start Date20 Dec 2024

Sponsor / Collaborator

Merck Healthcare KGaA

[+1]

NCT05464030

/ RecruitingPhase 1

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)

The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 in advanced solid tumors. This study contains 2 parts: Dose escalation (Part 1) and dose expansion (Part 2).
Study details include:
* Study Duration per participant: Approximately 4 months for Part 1 and 8 months for Part 2
* M9140 is not available through an expanded access program

Start Date04 Aug 2022

Sponsor / Collaborator

EMD Serono Research & Development Institute, Inc.

[+1]

100 Clinical Results associated with Precemtabart tocentecan

100 Translational Medicine associated with Precemtabart tocentecan

100 Patents (Medical) associated with Precemtabart tocentecan

Literatures (Medical) associated with Precemtabart tocentecan

01 Apr 2025·INTERNATIONAL JOURNAL OF TOXICOLOGY

The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients—The Putative Mechanism Behind ILD

Article

Author: Mueller, Gundi ; Vigna, Enrico ; Bertotti, Elisa ; Salve, Ilse De ; Onidi, Manuela ; Sloot, Willem N. ; Tavano, Patrizia ; Paoletti, Andrea

The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan. At 24 mg/kg or higher, transient reductions in neutrophil and reticulocyte counts were observed with each dosing event along with reversible anemia throughout the study. The no observed adverse effect level was 24 mg/kg and the maximum tolerated dose was 30 mg/kg. The difference in toxicity by this small dose increment was correlated with a 2.5-fold difference in plasma exatecan exposure indicating antigen-independent toxicity. As anticipated, no lung toxicity was found with M9140 in these studies that were similar in study design to those used to confirm ILD with trastuzumab-deruxtecan in monkeys. Since the non-human primate model is regarded as predictive for the ILD risk in humans, this result indicates a low risk for ILD when applying M9140 to patients. The current M9140 safety data are discussed with special focus on the absence or presence of ILD with other antibody camptothecin-conjugates, for which a hypothetical pathogenic mechanism is postulated here. The favorable nonclinical profile of M9140 warrants further investigation in patients with CEACAM5-overexpressing tumors.

NATURE MEDICINE

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

Article

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

Abstract:

CEACAM5, a cell surface protein, is overexpressed in colorectal cancer (CRC). Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody–drug conjugate with the topoisomerase 1 inhibitor exatecan as payload. Precem-TcT demonstrated strong antitumor activity and potent bystander activity in preclinical models. Its toxicity profile in cynomolgus monkeys was consistent with that of exatecan. 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). Primary endpoints were dose-limiting toxicities (DLTs), adverse events and preliminary clinical activity to establish the recommended dose(s) for expansion (RDEs). Secondary endpoints included pharmacokinetic parameters, objective response and median progression-free survival (mPFS). 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. A treatment-related death, also deemed disease related, was reported in a patient with multiple comorbidities and grade 3 obesity. 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), all at DLs ≥2.4 mg kg−1. mPFS was 5.9 months (95% confidence interval: 4.6–7.2); at DLs ≥2.4 mg kg−1 (n = 34), mPFS was 6.7 months (95% confidence interval: 4.6–8.8). Four patients (10.0%) remained on treatment at cutoff. These early clinical data corroborate preclinical findings, showing predictable safety and encouraging antitumor activity of Precem-TcT at DLs ≥2.4 mg kg−1, with no interstitial lung disease or ocular toxicity. 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.

News (Medical) associated with Precemtabart tocentecan

02 Jun 2025

·www.pharmaceutical-technology.com

ASCO25: MSD’s KRAS G12C drug shows early promise in Phase I

MSD investigated the KRAS G12C inhibitor in patients with solid tumours, including advanced colorectal cancer and non-small cell lung cancer. Image credit: Shutterstock / Atmosphere1. MSD’s investigational KRAS G12C inhibitor has shown signs of anti-tumour activity when used both alone and in combination with other oncology drugs. Announcing the data at the American Society of Clinical Oncology (ASCO) meeting 2025, being held from 30 May to 3 June in Chicago, MSD said that MK-1084 was also safe and tolerable in patients with solid tumours, including advanced colorectal cancer (CRC) and non-small cell lung cancer (NSCLC), in the Phase I KANDLELIT-001 trial (NCT05067283). In patients with CRC, there was a 38% confirmed overall response rate (ORR) in the monotherapy arm. When used in combination with Erbitux (cetuximab), there was a 46% confirmed ORR, and when used with both Erbitux and mFOLFOX6(oxaliplatin and leucovorin plus 5-fluorouracil), the confirmed ORR was 38%. Investigators also reported 43% unconfirmed ORR with MK-1084 alone, 56% in combination with Erbitux and 66% in combination with Erbitux and mFOLFOX6. In patients with NSCLC, there was an ORR of 38% in the monotherapy arm, 77% when it was used in combination with Keytruda (pembrolizumab), and 53% when used with Keytruda and chemotherapy (carboplatin and pemetrexed). In all arms, MSD states that MK-1084 had a manageable safety profile. Treatment-related adverse events (AEs) occurred in 58% of patients in the MK-1084 monotherapy arm; 94% of patients in the MK-1084 and Keytruda arm;, 93% of patients in the MK-1084, Keytruda and chemotherapy arm; 95% of patients in the MK-1084 and Erbitux arm; and 97% of patients in the MK-1084 with Erbitux and mFOLFOX6 arm. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence MSD Research Laboratories SVP and oncology, global clinical development Dr Marjorie Green said: “We are encouraged by the promising early data from the KANDLELIT-001 study and look forward to further researching the potential for MK-1084, as monotherapy or in combinations, including with Keytruda in certain settings in patients with KRAS mutations, which are among the most prevalent mutations in cancer.” MSD is also investigating the KRAS G12C in several Phase III trials, including the Phase III KANDLELIT-012 study in patients with unresectable or metastatic CRC with KRAS G12C-mutated tumours and the Phase III KANDLELIT-004 study in patients with NSCLC with KRAS G12C-mutated tumours that express PD-L1 (NCT06345729). ASCO updates MSD also reported data from a Phase II/III study of zilovertamab vedotin as a combination therapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study achieved a 56.3% ORR. Other major pharmaceutical companies have also revealed data around the ASCO 2025 conference. Pfizer announced data from its Phase III BREAKWATER study of Braftovi (encorafenib) in combination with Erbitux and mFOLFOX6. Merck KGaA also highlighted success in two studies, a Phase III trial of its CSF-1R inhibitor pimicotinib in tenosynovial giant cell tumour (TGCT) patients and a Phase I study of M9140, a CEACAM5-targeting antibody-drug conjugate (ADC), in patients with metastatic CRC . Pharmaceutical Technology Excellence Awards - Have you nominated? Nominations are now open for the prestigious Pharmaceutical Technology Excellence Awards - one of the industry's most recognised programmes celebrating innovation, leadership, and impact . This is your chance to showcase your achievements, highlight industry advancements , and gain global recognition . Don't miss the opportunity to be honoured among the best - submit your nomination today! Nominate Now

Phase 1ASCOClinical ResultPhase 3ADC

28 Apr 2025

·www.pharmaceutical-technology.com

Merck KGaA strikes $3.9bn deal for SpringWorks

Merck KGaA has sealed a $3.9bn deal to acquire SpringWorks. Credit: LumiNola via Getty Images. Merck KGaA (Merck) has moved to strengthen its position in oncology and rare diseases with a $3.9bn agreement to acquire SpringWorks Therapeutics. Under the deal, Merck will pay $47 per share in cash, representing a 26% premium to SpringWorks’ average share price over the 20 days leading up to 7 February 2025, the day before media reports of the potential acquisition surfaced. Based on SpringWorks’ cash holdings at the end of 2024, the deal gives the company an enterprise value of approximately $3.4bn. Headquartered in Darmstadt, Germany, Merck said the acquisition would “immediately add revenue” and strengthen its oncology pipeline in the 28 April announcement. The deal will bolster Merck’s oncology portfolio with US-based SpringWorks’ pipeline of targeted therapies. These include Ogsiveo (nirogacestat), which is approved for treating desmoid tumours; as well as the MEK inhibitor Gomekli (mirdametinib), which was approved in February 2025 for treating neurofibromatosis type 1 (NF1). Ogsiveo generated $172m in sales in 2024, as per the company’s financials. According to projections from GlobalData’s Pharma Intelligence Center, Gomekli is projected to generate up to $564m in global sales by 2030 while Ogsiveo sales are expected to reach $1.2bn by the same year. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence GlobalData is the parent company of Pharmaceutical Technology. In a statement, Merck’s CEO Belén Garijo said: “The agreed acquisition of SpringWorks is a major step in our active portfolio strategy to position our company as a globally diversified, innovation and technology powerhouse. “For our healthcare sector, it sharpens the focus on rare tumours, accelerates growth, and strengthens our presence in the US.” Late-stage talks between the companies were confirmed last week following several months of speculation. Reuters first reported in February 2025 that Merck was exploring a potential deal, triggering a 34% rise in SpringWorks’ share price. Merck KGaA acknowledged the discussions at the time but cautioned that there was no certainty that an agreement would be reached. The acquisition marks the second deal for Merck in the space of a month. At the beginning of April, the company signed a $1.4bn multi-year collaboration with Caris Life Sciences to access novel antibody-drug conjugate (ADC) targets. Under the agreement, Caris will identify tumour-associated targets that Merck will take into preclinical and clinical development. Merck’s lead internal ADC candidate M9140 is currently in Phase I trials for colorectal cancer. Merck expects the SpringWorks acquisition to close in H2 2025, subject to regulatory and customary approvals. “Beyond this planned transaction, we will continue to explore M&A opportunities across our three complementary business sectors, always with a firm focus on strategic fit, financial robustness, and long-term value creation,” Garijo concluded.

Drug ApprovalPhase 1AcquisitionADC

25 Apr 2025

·www.pharmaceutical-technology.com

Merck KGaA nears $3.5bn deal for SpringWorks

Merck KGaA is in late-stage discussions to acquire SpringWorks. Credit: Anne Czichos via Getty Images. Merck KGaA is edging closer to the SpringWorks deal, which was first rumoured in February, confirming late-stage negotiations at an estimated price of $47 per share – potentially valuing the deal at around $3.5bn. The company confirmed in a 24 April statement that while no final, legally binding agreement has been established, the “parties are in discussion on the basis of a price of around $47 per share.” The news follows months of speculation. Market chatter around a potential acquisition began on 10 February 2025, when Reuters reported that Merck KGaA was exploring a deal. That same day, the German pharma firm acknowledged the discussions, but cautioned that there was no guarantee of a transaction. Following the report, SpringWorks shares jumped 34%, pushing the company’s market capitalisation over $4bn. Merck KGaA’s CEO Belén Garijobut declined to provide updates on the deal during the company’s full-year earnings press call in March, keeping investors in suspense. Shares in SpringWorks were up by almost 9% when the markets opened on 25 April, after the latest development. A successful acquisition would bolster Merck KGaA’s oncology portfolio with SpringWork’s pipeline of targeted therapies. These include Ogsiveo (nirogacestat), which is approved for treating desmoid tumours, as well as the MEK inhibitor Gomekli (mirdametinib), which was approved in February 2025 for treating neurofibromatosis type 1 (NF1), a rare genetic disorder. According to projections from GlobalData’s Pharma Intelligence Center, Gomekli is projected to generate up to $564m in global sales by 2030, while Ogsiveo sales are expected to reach $1.2bn by the same year. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence GlobalData is the parent company of Pharmaceutical Technology. Merck KGaA already has a strong oncology pipeline. Its top-selling product in 2024 was Erbitux (cetuximab), which generated €1.16bn ($1.25bn) in revenue. The drug is a monoclonal antibody used to treat certain head and neck cancers, and colorectal cancer. However, not all programs have been as successful. In June 2024, Merck KGaA terminated the Phase III TrilynX clinical trial of xevinapant after the drug failed to significantly improve survival in patients with locally advanced head and neck cancer. Additionally, Merck KGaA has faced setbacks in its neurology pipeline, including the discontinuation of BTK inhibitor evobrutinib in March 2024. The decision followed two Phase II trials in relapsing multiple sclerosis, where the drug did not achieve a statistically significant reduction in annual relapse rates compared to Sanofi’s Aubagio (teriflunomide). The programme had already come under scrutiny in April 2023, when the US Food and Drug Administration (FDA) placed a partial clinical hold on a Phase III study after cases of liver injury were reported. Merck KGaA has continued to prioritise the expansion of its oncology portfolio. Earlier in April 2025, the company signed a $1.4bn multi-year collaboration with Caris Life Sciences to access novel antibody-drug conjugate (ADC) targets. Under the agreement, Caris will identify tumour-associated targets, which Merck KGaA will take into preclinical and clinical development. Merck KGaA also has an internal ADC programme, with its lead candidate M9140 currently in Phase I trials for colorectal cancer.

Drug ApprovalPhase 2AcquisitionPhase 1Phase 3

100 Deals associated with Precemtabart tocentecan

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
metastatic non-small cell lung cancer	Phase 2	United States	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	China	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	Japan	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	Australia	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	Austria	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	France	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	Germany	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	Italy	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	South Korea	Merck Healthcare KGaA	26 Mar 2025
metastatic non-small cell lung cancer	Phase 2	Spain	Merck Healthcare KGaA	26 Mar 2025

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05464030 (PROCEADE-CRC-01, Pubmed) Manual	Phase 1	Metastatic Colorectal Carcinoma	40	Precemtabart tocentecan (Dose escalation (0.6-3.2 mg kg−1))	hsvrcibmep(olfhzianjg) = zqhejzroef mizweabglk (gugeszmaar ) View more	Positive	30 Jul 2025
NCT05464030 (PROCEADE CRC-01, ASCO2025) Manual	Phase 1	Metastatic Colorectal Carcinoma	60	Precemtabart tocentecanPrecemtabart tocentecan 2.8 mg/kg Q3W	zyshhmpijj(lclhkvalry) = ljuhvnrmke jatormseyu (tjxbiqgvcv ) View more	Positive	30 May 2025
NCT05464030 (PROCEADE CRC-01, ASCO2025) Manual	Phase 1	Metastatic Colorectal Carcinoma	60	Precemtabart tocentecanPrecemtabart tocentecan 2.4 mg/kg Q3W	zyshhmpijj(lclhkvalry) = mvxfozvsaq jatormseyu (tjxbiqgvcv ) View more	Positive	30 May 2025
NCT05464030 (ESMO2024) Manual	Phase 1	Metastatic Colorectal Carcinoma Third line KRAS \| NRAS \| BRAF mutation status	40	M9140 ≥2.4 mg/kg	csxqgzsczo(zjeyysnbry) = bwmusdkypn rvwbludakn (fkcrjfmflz ) View more	Positive	16 Sep 2024
NCT05464030 (ESMO2024) Manual	Phase 1		40	M9140 <2.4 mg/kg	csxqgzsczo(zjeyysnbry) = bgcgkevkix rvwbludakn (fkcrjfmflz ) View more	Positive	16 Sep 2024
NCT05464030 (ASCO2024) Manual	Phase 1	Metastatic Colorectal Carcinoma	40	M9140M9140 2.8 mg/kg	urqxpfecfw(dofexytxkk) = ceyskbzgop pwizkqxkup (yplbkyhgqh ) View more	Positive	24 May 2024

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