M9140 for Colorectal Cancer

Recruiting at 35 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

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called M9140 to see if it is safe and effective for patients with advanced solid tumors. Researchers will study how the drug behaves in the body, how well patients can tolerate it, and if it shows any signs of fighting the cancer.

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.

What data supports the effectiveness of the drug M9140 for colorectal cancer?

Research shows that targeting CEACAM5, a protein often found in high amounts in colorectal cancer cells, with antibody-drug conjugates (ADCs) can effectively inhibit tumor growth. Similar treatments, like the anti-CEACAM5 ADCs described in studies, have shown promising results in reducing tumor size in preclinical models. ^{1 2 3 4 5}

What safety data exists for M9140 or similar treatments targeting CEACAM5?

Research on similar treatments targeting CEACAM5, like antibody-drug conjugates, shows they can inhibit tumor growth without significant side effects, such as changes in body weight, in animal studies. However, specific safety data for M9140 in humans is not available from the provided research. ^{1 2 3 6 7}

What makes the drug M9140 unique for treating colorectal cancer?

M9140 is an antibody-drug conjugate (ADC) that targets CEACAM5, a protein overexpressed in many cancers, including colorectal cancer. This drug combines an antibody that specifically binds to CEACAM5 with a cytotoxic agent, allowing it to deliver the drug directly to cancer cells, potentially reducing side effects and improving effectiveness compared to traditional chemotherapy. ^{1 2 4 6 8}

Research Team

Medical Responsible

Principal Investigator

EMD Serono Research & Development Institute, Inc.

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity. [2022]

4. United States 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. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Novel protein isoforms of carcinoembryonic antigen are secreted from pancreatic, gastric and colorectal cancer cells. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

CEACAM1 and hollow spheroid formation modulate the chemosensitivity of colorectal cancer to 5-fluorouracil. [2015]

7. Ireland 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. [2022]

8. United States 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. [2022]