M9140 for Colorectal Cancer

Recruiting at 46 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: EMD Serono Research & Development Institute, Inc.

Disqualifiers: Brain metastases, Chronic inflammatory bowel disease, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment, M9140 (an experimental drug), to determine its safety and effectiveness for individuals with advanced colorectal cancer unresponsive to standard treatments. Participants may receive M9140 alone or in combination with other drugs, such as Bevacizumab and 5-fluorouracil. Suitable candidates have advanced colorectal cancer that has progressed despite other treatments. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that M9140 has a manageable and predictable safety profile based on previous studies. In trials with patients who had already received several treatments for colorectal cancer, M9140 was generally well-tolerated. Researchers determined that the safest dose was about 2.8 mg per kilogram of body weight, indicating a dose that worked effectively while remaining safe. Although some side effects were reported, they were considered manageable. This suggests that M9140 could be a safe option for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for colorectal cancer?

Researchers are excited about M9140 for colorectal cancer because it offers a new approach compared to the standard treatments like chemotherapy and targeted therapies. Unlike traditional options, M9140 might work by targeting specific pathways involved in cancer growth, potentially offering a more precise attack on cancer cells. This drug is also being tested in combination with other agents like Bevacizumab and 5-fluorouracil, which could enhance its effectiveness and provide better outcomes for patients. These combinations are promising because they might reduce the side effects associated with conventional therapies and improve overall treatment results.

What evidence suggests that M9140 could be an effective treatment for colorectal cancer?

Research has shown that M9140, a new drug, holds promise for treating advanced solid tumors, including metastatic colorectal cancer. Early studies found that it controlled tumor growth in about 72.4% and 67.7% of patients in different groups after 12 weeks. This trial will evaluate M9140 in various treatment arms, including combinations with Bevacizumab, Capecitabine, 5-fluorouracil, and Folinic acid. Initial findings also indicate that M9140's side effects are predictable and manageable, which is important for patients. While more research is needed, these early results offer encouragement for those considering this treatment. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

EMD Serono Research & Development Institute, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer who've had no luck or bad reactions to standard treatments. They must be in good physical shape (ECOG PS < 1), and have their major organs working well. It's not for those with recent other cancers, brain metastases causing symptoms, chronic bowel inflammation, serious heart issues within the past 6 months, or certain severe digestive problems.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My blood, liver, and kidney functions meet the study's requirements.

Other protocol defined inclusion criteria could apply

Exclusion Criteria

Other protocol defined exclusion criteria could apply

I have not had a stroke in the last 6 months.

I haven't had recent serious heart issues or a heart procedure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part 1)

Participants receive escalating doses of M9140 to evaluate safety and tolerability

4 months

Dose Expansion (Part 2)

Participants receive M9140 in combination with other drugs to further evaluate safety and clinical activity

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• M9140

Trial Overview

The study tests M9140, a new drug aimed at solid tumors like colorectal cancer. Participants will also receive Bevacizumab and Capecitabine. The trial has two parts: first finding the right dose of M9140 (Part 1) and then seeing how well it works at that dose (Part 2).

How Is the Trial Designed?

Group I: Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab Experimental Treatment 3 Interventions

Group II: Part 2C: M9140 + Bevacizumab +/-Capecitabine Experimental Treatment 3 Interventions

Group III: Part 2B: M9140 Experimental Treatment 1 Intervention

Group IV: Part 2A: M9140 Experimental Treatment 1 Intervention

Group V: Part 1: M9140 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

Published Research Related to This Trial

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]

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]

Colorectal cancer cells expressing the CEACAM1-4L isoform showed significantly higher resistance to the chemotherapy drug 5-fluorouracil (5FU), indicating that the balance of CEACAM1 isoforms can influence treatment outcomes.

The presence of hollow spheroids (HS) in colorectal cancer patients was identified as an independent risk factor for recurrence after surgery and 5FU-based chemotherapy, suggesting that HS formation may contribute to poorer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CEACAM1 and hollow spheroid formation modulate the chemosensitivity of colorectal cancer to 5-fluorouracil. Yamamoto, N., Yokoyama, S., Ieda, J., et al.[2015]

The novel anti-CEACAM5 monoclonal antibody, mAb CC4, shows strong specificity for colorectal cancer tissues and effectively inhibits tumor growth in xenografted mice, indicating its potential as a targeted cancer therapy.

mAb CC4 enhances the immune response by increasing natural killer (NK) cell activity against colorectal cancer cells, particularly those lacking MHC-I, suggesting it could be a promising treatment option that boosts the body's own defenses against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity. Zheng, C., Feng, J., Lu, D., et al.[2022]

In a study of 265 patients with operable colorectal cancer, 37% had detectable circulating CEACAM5mRNA-positive cells, which were linked to worse clinical outcomes.

The presence of these cells was associated with higher relapse rates, decreased disease-free survival, and lower overall survival, making them an independent prognostic factor for poor outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of the detection of peripheral blood CEACAM5mRNA-positive cells by real-time polymerase chain reaction in operable colorectal cancer. Vardakis, N., Messaritakis, I., Papadaki, C., et al.[2011]

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]

COMP expression is significantly higher in colon cancer tissues, especially in advanced stages (I to IV), and is associated with poorer survival outcomes, making it a potential biomarker for disease progression.

Compared to the traditional biomarker CEACAM5, COMP shows stronger predictive value across different cancer stages and molecular subtypes, suggesting it may be a more effective indicator for colon cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cartilage Oligomeric Matrix Protein, COMP may be a Better Prognostic Marker Than CEACAM5 and Correlates With Colon Cancer Molecular Subtypes, Tumor Aggressiveness and Overall Survival. Wusterbarth, E., Chen, Y., Jecius, H., et al.[2022]

A new fully-human anti-CEACAM5 monoclonal antibody, 1G9, has been developed, showing high specificity and affinity for the CEACAM5 protein, which is a potential marker for neuro-endocrine prostate cancer (NEPC).

The antibody demonstrated effective antibody-dependent cellular cytotoxicity (ADCC) against CEACAM5-positive prostate cancer cells and CAR-T cells based on 1G9 showed strong antitumor activity in mouse models, indicating its potential as a therapeutic option for NEPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A highly-specific fully-human antibody and CAR-T cells targeting CD66e/CEACAM5 are cytotoxic for CD66e-expressing cancer cells in vitro and in vivo. Baek, DS., Kim, YJ., Vergara, S., et al.[2022]

Citations

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nature.com

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However, the overall efficacy of current treatment options in later lines is limited, with a median overall survival of less than 12 months, ...

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Precemtabart tocentecan (M9140), an anti-CEACAM5 ADC ...

DCR at 12 weeks was 72.4% in A1 and 67.7% in A2. Conclusions: These preliminary results corroborate the encouraging efficacy and safety data ...

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ascopubs.org

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First-in-human trial of M9140, an anti-CEACAM5 antibody ...

First-in-human trial of M9140, an anti-CEACAM5 antibody drug conjugate (ADC) with exatecan payload, in patients (pts) with metastatic colorectal ...

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Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors ...

The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 in advanced ...

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Precem-TcT has demonstrated promising efficacy and a predictable and manageable safety profile in pts with advanced CRC (Phase 1). Preclinical data suggest that ...

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aacrjournals.org

aacrjournals.org/cancerres/article/84/6_Supplement/2362/738805/Abstract-2362-Preclinical-efficacy-and-safety-of

Abstract 2362: Preclinical efficacy and safety of M9140, a ...

The TOP1 inhibitor-based ADC M9140 caused strong antitumor efficacy with a tumor volume reduction of 74% and 88% as best response in two CRC PDX ...

7.

mdanderson.org

mdanderson.org/newsroom/asco-novel-targeted-cancer-therapies-demonstrate-activity-safety-metastatic-solid-tumors.h00-159697545.html

ASCO: Novel targeted cancer therapies demonstrate ...

... ADCs. The data suggest that M9140 has a manageable safety profile, leading researchers to determine the maximum tolerated dose at 2.8 mg/kg ...

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annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)02161-6/fulltext

573P M9140, an anti-CEACAM5 antibody drug conjugate ...

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.