M9140 for Solid Tumors

Recruiting at 5 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

Trial Summary

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.

What data supports the effectiveness of the drug M9140 for solid tumors?

Research on similar treatments, like SAR408701 and other antibody-drug conjugates targeting CEACAM5, shows promising results in preclinical studies, effectively targeting and killing cancer cells in various types of tumors that overexpress CEACAM5. ^{1 2 3 4 5}

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

In a study using a similar treatment targeting CEACAM5, mice showed no significant change in body weight, suggesting it might be safe. However, this data is from preclinical studies, so more research is needed to confirm safety in humans. ^{1 2 3 5 6}

How is the drug M9140 different from other treatments for solid tumors?

M9140 is unique because it is an antibody-drug conjugate (ADC) that specifically targets CEACAM5, a protein overexpressed in many cancers, allowing it to deliver a cytotoxic drug directly to tumor cells, potentially reducing side effects on normal tissues. ^{1 3 5 7 8}

What is the purpose of this trial?

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).

Research Team

Medical Responsible

Principal Investigator

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

Eligibility Criteria

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.

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

Other protocol defined inclusion criteria could apply

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

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)

Treatment Details

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.

Participant Groups

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

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]

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 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]

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 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]

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]

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]

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

The old CEACAMs find their new role in tumor immunotherapy. [2023]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration. [2022]

5. Switzerland 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. [2023]

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

Evaluation of novel anti-CEACAM6 antibody-based conjugates for radioimmunotheranostics of pancreatic ductal adenocarcinoma. [2023]

7. Ireland 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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