M9140 for Solid Tumors

Recruiting at 70 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: EMD Serono Research & Development Institute, Inc.

Must not be taking: Irinotecan

Disqualifiers: Recent malignancy, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 8-12 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called M9140 (an antibody-drug conjugate) for certain advanced cancers, including gastric, non-small cell lung, and pancreatic cancers. Researchers aim to determine how well M9140 works on tumors with a specific protein called CEACAM5. The trial will also assess the safety and metabolism of the drug when used alone or with other treatments. Individuals with these cancers, who have tried other treatments without success, and whose tumors express CEACAM5 might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have progressed after certain systemic therapies, which might imply that some treatments could be continued. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that M9140 has been tested for safety and tolerability in treating certain cancers. In earlier studies, patients did not experience serious lung or eye problems, and no deaths were directly linked to the treatment. These findings suggest that M9140 is generally safe at the tested doses, with manageable side effects. However, ongoing research will continue to provide more information about its safety. Prospective trial participants should consult a healthcare provider for personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

M9140 is unique because it targets solid tumors by focusing on CEACAM5, a protein often found in high levels in certain cancers. Unlike standard treatments like chemotherapy or targeted therapies that may not specifically address this protein, M9140's mechanism aims directly at cells expressing CEACAM5. This could mean more precise targeting of cancer cells and potentially fewer side effects. Researchers are excited about M9140 because it could offer a new option for patients whose tumors express this protein, particularly in hard-to-treat cancers like gastric and pancreatic cancers.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that M9140 may help treat tumors with a protein called CEACAM5, found in some cancers. Early results suggest it can target and destroy cancer cells without causing serious side effects like lung or eye problems. In studies with patients who had colorectal cancer, M9140 shrank tumors. This trial includes various treatment arms where participants will receive M9140 monotherapy, targeting different cancer types such as advanced stomach, lung, and pancreatic cancers. This treatment combines an antibody with chemotherapy to specifically attack cancer cells while leaving most healthy cells unharmed. These findings are promising for people with these advanced cancers. ^{1 3 4 5 6}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Are You a Good Fit for This Trial?

This trial is for adults with advanced gastric, non-small cell lung, or pancreatic cancer that shows the presence of a specific protein called CEACAM5. Participants should have tumors that are locally advanced or have spread (metastatic).

Inclusion Criteria

I am able to understand and sign the consent form.

Other protocol defined inclusion criteria could apply

I am fully active or have some restrictions but can still carry out light work.

Exclusion Criteria

I have brain metastases but meet certain criteria for treatment.

I have been treated with irinotecan before.

I have moderate to severe diarrhea or bowel obstruction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive M9140 infusion on Day 1 of every cycle

8-12 months

Monthly visits for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• M9140

Trial Overview The PROCEADE PanTumor study tests M9140, an antibody-drug conjugate targeting CEACAM5. It's given either alone or with other treatments to see how well it works and what its safety profile is like across different types of cancer.

How Is the Trial Designed?

Group I: Substudy PDAC: M9140 Monotherapy - Part A CEACAM5 High Experimental Treatment 1 Intervention

Group II: Substudy NSCLC: M9140 Monotherapy - Part B CEACAM5 High EGFR mut Experimental Treatment 1 Intervention

Group III: Substudy NSCLC: M9140 Monotherapy - Part A CEACAM5 High EGFR Wt Experimental Treatment 1 Intervention

Group IV: Substudy GC: M9140 Monotherapy - Part B CEACAM5 Low Experimental Treatment 1 Intervention

Group V: Substudy GC: M9140 Monotherapy - Part A CEACAM5 High Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

60

Recruited

7,900+

Danny Bar-Zohar

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Chief Executive Officer

MD

Danny Bar-Zohar

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

CEACAMs, particularly CEA (CEACAM5), are important tumor biomarkers and are being explored for their roles in cancer diagnosis, prognosis, and treatment, highlighting their diverse expression in normal and tumor tissues.

Recent clinical studies on CEA-targeted cancer immunotherapies, such as bispecific antibodies and CAR-T cells, show promising potential for improving cancer treatment, although challenges remain in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The old CEACAMs find their new role in tumor immunotherapy. Han, ZW., Lyv, ZW., Cui, B., et al.[2023]

The antibody-drug conjugate SAR408701 specifically targets CEACAM5, which is overexpressed in various cancers, and shows strong binding affinity to both human and cynomolgus monkey CEACAM5, indicating its potential for selective cancer therapy.

Preclinical studies demonstrated that SAR408701 effectively kills CEACAM5-expressing tumor cells and shows promising in vivo efficacy in mouse models, with a toxicity profile similar to that of the drug DM4 alone, suggesting a favorable safety profile for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Activity of SAR408701: A Novel Anti-CEACAM5-maytansinoid Antibody-drug Conjugate for the Treatment of CEACAM5-positive Epithelial Tumors. Decary, S., Berne, PF., Nicolazzi, C., et al.[2022]

The study developed CAR-T cells that specifically target CEACAM5, showing effective tumor reduction in both CEACAM5-expressing non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) models, indicating a promising therapeutic strategy.

Unlike antibody-drug conjugates (ADCs), which showed cytotoxicity regardless of CEACAM5 levels, the CAR-T cells demonstrated a concentration-dependent effect, suggesting they may be more effective in cases where CEACAM5 is highly expressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells are effective against CEACAM5 expressing non-small cell lung cancer cells resistant to antibody-drug conjugates. Kim, YJ., Li, W., Zhelev, DV., et al.[2023]

CEACAM5 is overexpressed in non-small-cell lung cancer (NSCLC) tissues and is associated with aggressive clinicopathological features, such as tumor size and lymph invasion, indicating its potential role in cancer progression.

Depleting CEACAM5 in NSCLC cells reduces their proliferation and migration by activating the p38-Smad2/3 signaling pathway, suggesting that targeting CEACAM5 could be a promising therapeutic strategy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration. Zhang, X., Han, X., Zuo, P., et al.[2022]

The study developed a fully human single-domain antibody (UdAb) targeting CEACAM5, which is overexpressed in various cancers, and demonstrated its potential as an effective delivery system for the cytotoxic agent monomethyl auristatin E (MMAE).

The UdAb-MMAE conjugate showed strong antitumor efficacy in multiple cancer cell lines and significantly inhibited tumor growth in mouse models without causing significant weight loss, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity. Zhu, XY., Li, QX., Kong, Y., et al.[2023]

Tusamitamab ravtansine, an antibody-drug conjugate targeting CEACAM5, shows promising efficacy in treating nonsquamous non-small cell lung cancer (NSQ-NSCLC) with high CEACAM5 expression, as evidenced by a 62.5% response rate in patient-derived xenograft models with high expression compared to 25% in those with lower expression.

CEACAM5 high expression (HE) was found in 24.3% of NSQ-NSCLC tumors, with higher prevalence in tumors with KRAS mutations and those with low or negative PD-L1 expression, suggesting that CEACAM5 could be a valuable target for treatment in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The search for therapeutic targets in lung cancer: Preclinical and human studies of carcinoembryonic antigen-related cell adhesion molecule 5 expression and its associated molecular landscape. Lefebvre, AM., Adam, J., Nicolazzi, C., et al.[2023]

This study identified two novel splice variants of the carcinoembryonic antigen (CEACAM5) in gastrointestinal cancer cell lines, which may enhance our understanding of cancer biology.

The research suggests that distinguishing between the full-length CEACAM5 protein and its novel isoforms could improve the effectiveness of CEA as a tumor marker in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel protein isoforms of carcinoembryonic antigen are secreted from pancreatic, gastric and colorectal cancer cells. Hatakeyama, K., Wakabayashi-Nakao, K., Ohshima, K., et al.[2021]

The novel CEACAM6-targeting antibody NY004 demonstrated high specificity and efficiency for imaging pancreatic ductal adenocarcinoma (PDAC) tumors, with significant tumor uptake and retention lasting up to 6 days post-injection, making it a promising tool for diagnostic imaging.

The radionuclide-labeled antibody [177Lu]-NY004 showed effective anti-tumor efficacy in PDAC models, characterized by high tumor uptake, low uptake in non-target organs, and prolonged retention, indicating its potential as a therapeutic option for CEACAM6-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of novel anti-CEACAM6 antibody-based conjugates for radioimmunotheranostics of pancreatic ductal adenocarcinoma. Kong, Y., Xie, F., Zhang, Z., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06710132

NCT06710132 | Study of Anti-CEACAM5 ADC M9140 in ... This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult ...

2. emdserono.com emdserono.com/us-en/company/news/press-releases/asco-2025-22-05-2025.html

ASCO 2025 The company today announced the presentation of new oncology data across more than 12 tumor types at the 2025 American Society of Clinical Oncology (ASCO) ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2025-04957

Study of Anti-CEACAM5 ADC M9140 in Participants With ... This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)01215-3/pdf

1O Precemtabart tocentecan (M9140) No interstitial lung disease, ocular toxicities, or treatment-related deaths were reported. In an independent analysis of tumor samples (s) from pts with CRC, ...

5. biospace.com biospace.com/press-releases/merck-showcases-innovation-in-advanced-cancers-and-rare-tumors-at-asco-2025

Merck Showcases Innovation in Advanced Cancers and ... Data from Phase 3 MANEUVER study demonstrating significant improvements in physical function and symptoms in patients with tenosynovial ...

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06710132/

Trial | NCT06710132 The PROCEADE PanTumor study aims to investigate M9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 ...