M3554 for Solid Tumors

Recruiting at 13 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: EMD Serono Research & Development Institute, Inc.

Disqualifiers: Other malignancies, Brain metastasis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3 months

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called M3554 for individuals with certain solid tumors, specifically soft tissue sarcoma (STS) and glioblastoma. The main goal is to determine the optimal dose and assess the treatment's safety, while also identifying any signs of effectiveness against these cancers. The trial targets those whose STS has worsened despite previous treatment or whose glioblastoma has returned after initial therapy. Participants should have undergone at least one prior treatment for their condition and still have some residual disease after surgery, if applicable. The study lasts about four months for each participant. As a Phase 1 trial, this research aims to understand 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 whether 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 M3554 is likely to be safe for humans?

Research shows that M3554, a new treatment for certain solid tumors, is being tested to determine the optimal dose and assess its safety. As this is an early study, detailed information about its safety for humans remains limited. However, this phase of research helps determine how well people tolerate the treatment and identify any side effects.

As one of the initial studies with M3554, researchers are still gathering information about its safety and potential side effects. Participants in this study will help establish the recommended dose and provide early insights into the treatment's safety and potential benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

M3554 is unique because it targets solid tumors in a way that is different from the current standard treatments, such as chemotherapy or radiation, which often affect both healthy and cancerous cells. Researchers are excited about M3554 because it potentially offers a more targeted approach, minimizing damage to healthy tissues and reducing side effects. This treatment could lead to better outcomes and improved quality of life for patients with solid tumors.

What evidence suggests that M3554 might be an effective treatment for solid tumors?

Research has shown that M3554, which participants in this trial will receive, is a promising treatment for solid tumors. This medicine is an anti-GD2 antibody-drug conjugate (ADC). Studies have found that these ADCs can effectively target and destroy cancer cells in solid tumors, such as neuroblastoma and other cancers with high levels of GD2. M3554 attaches to the GD2 protein on cancer cells and delivers a toxic drug directly to them, helping to shrink the tumor. Early results suggest that M3554 is very effective against tumors, offering hope for patients with soft tissue sarcoma and glioblastoma. ^{1 4 5 6 7}

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 specific advanced solid tumors: glioblastoma, IDH-wildtype after one prior therapy and soft tissue sarcoma (STS) that's worsened after treatment. Participants must have good blood, liver, and kidney function, an ECOG Performance Status of 1 or less, and can't have had certain other cancers in the last 3 years.

Inclusion Criteria

Other protocol defined inclusion criteria could apply

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

I have glioblastoma, IDH-wildtype, and it has worsened after just one treatment.

Exclusion Criteria

Other protocol defined exclusion criteria could apply

I haven't had cancer other than skin cancer, cervical carcinoma in situ, or benign prostate issues in the last 3 years.

I have a history of brain or spinal cord cancer spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive M3554 monotherapy to establish recommended doses and evaluate safety and preliminary antitumor activity

Approximately 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• M3554

Trial Overview The study tests M3554 to find safe doses and see if it helps against tumors. It targets people with STS or glioblastoma who've tried other treatments without success. The trial lasts about 4 months per participant.

How Is the Trial Designed?

Group I: Dose Escalation: M3554 Monotherapy 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

This study is the first to demonstrate the effectiveness of anti-GD2 antibody-drug conjugates (ADCs) in targeting solid tumors, showing significant cytotoxic effects in GD2-positive cancer cell lines and mouse models.

The ADCs, ch14.18-MMAE and ch14.18-MMAF, were effective in reducing tumor size significantly in mouse models, with ch14.18-MMAF showing superior efficacy in high GD2-expressing cells, indicating their potential for treating various GD2-expressing solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors. Kalinovsky, DV., Kibardin, AV., Kholodenko, IV., et al.[2022]

The combination of anti-GD2 and anti-CD47 antibodies demonstrates a synergistic effect in treating neuroblastoma and osteosarcoma, suggesting a promising therapeutic strategy for these cancers.

This synergy indicates that using both antibodies together may enhance the immune response against tumor cells, potentially improving treatment outcomes for patients with these types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GD2 and Anti-CD47 Are Synergistic and Promote Tumor Eradication. [2022]

The humanized anti-GD2 antibody hu3F8-IgG1 demonstrated significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) compared to the original murine antibody m3F8, suggesting improved efficacy in targeting neuroblastoma.

In vivo studies showed that hu3F8-IgG1 had better anti-tumor effects against neuroblastoma xenografts than m3F8, while also minimizing potential side effects like pain and human anti-mouse antibody (HAMA) responses, indicating a promising direction for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humanizing murine IgG3 anti-GD2 antibody m3F8 substantially improves antibody-dependent cell-mediated cytotoxicity while retaining targeting in vivo. Cheung, NK., Guo, H., Hu, J., et al.[2023]

Ganglioside GD2 is a safe and effective target for antibody therapy in treating various cancers, particularly high-risk metastatic neuroblastoma, due to its limited presence in normal tissues.

Current research is expanding on anti-GD2 therapies by exploring novel combinations of antibodies, cytokines, and genetically engineered products, indicating a promising future for immunotherapy targeting GD2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2-targeted immunotherapy and radioimmunotherapy. Dobrenkov, K., Cheung, NK.[2021]

In a study involving patients treated with GD2-targeting CAR T cells, 75% experienced both radiographic and clinical improvements, indicating a strong efficacy of this treatment approach.

The results suggest that GD2-targeting CAR T cell therapy could be a promising option for patients, potentially leading to significant positive outcomes in their cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2-Targeting CAR T Cells Show Promise in H3K27M-Mutated Gliomas. [2022]

In a study of 386 breast cancer cases, 35% showed positive expression of the GD2 antigen, which is associated with certain tumor characteristics like low grade and estrogen receptor positivity.

While GD2 expression correlated with specific clinicopathologic features, it did not significantly impact event-free or overall survival, suggesting that while GD2 could be a useful biomarker, its role in prognosis may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma: Clinical and Pathologic Correlation. Zhong, E., Brogi, E., D'Alfonso, TM., et al.[2023]

Dinutuximab, an anti-GD2 monoclonal antibody, has been approved by the FDA for treating high-risk neuroblastoma in children, highlighting its efficacy as a targeted cancer immunotherapy.

Anti-GD2 mAbs work through various mechanisms to kill tumor cells and can be used alone or in combination with other treatments to enhance their antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy. Perez Horta, Z., Goldberg, JL., Sondel, PM.[2019]

Ganglioside GD2 is a promising target for immunotherapy in various tumors, especially neuroectoderm-derived cancers like neuroblastoma and melanoma, due to its limited expression in normal tissues, making it safer for targeted treatment.

Anti-GD2 antibodies have shown proven safety and efficacy in clinical trials, but challenges such as pain toxicity and the inability to treat bulky tumors have led to the development of innovative strategies to enhance treatment effectiveness and reduce side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. Ahmed, M., Cheung, NK.[2022]

GD2 is identified as a specific target antigen for breast cancer stem-like cells, particularly in triple-negative breast cancer, and targeting it with GD2-CAR T cells shows promise in halting tumor progression and preventing metastasis in preclinical models.

The GD2-CAR T cells demonstrated effective activation and expansion in tumor environments without signs of exhaustion, indicating a potentially safer and more effective immunotherapy approach for treating GD2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2-targeted chimeric antigen receptor T cells prevent metastasis formation by elimination of breast cancer stem-like cells. Seitz, CM., Schroeder, S., Knopf, P., et al.[2022]

In a phase I trial involving 12 patients with GD2 antigen-positive metastatic melanoma, the murine anti-GD2 monoclonal antibody 14G2a showed very modest antitumor activity, with only one patient achieving a partial response.

The treatment was associated with significant neurological toxicity, including reversible motor neuropathy and other side effects, which may limit its clinical use, especially at doses greater than 80 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma. Saleh, MN., Khazaeli, MB., Wheeler, RH., et al.[2007]

In a study of 1102 patients undergoing GD2-directed immunotherapy with dinutuximab beta, 4.0% experienced severe neurotoxicities, particularly those receiving the drug in combination with subcutaneous interleukin-2 (scIL-2).

While most patients showed neurological recovery after treatment for neurotoxicity, 0.45% had persistent severe neurological deficits, leading to the recommendation against using scIL-2 with dinutuximab beta due to its lack of clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Phenotype and Management of Severe Neurotoxicity Observed in Patients with Neuroblastoma Treated with Dinutuximab Beta in Clinical Trials. Wieczorek, A., Manzitti, C., Garaventa, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06641908

Study Details | NCT06641908 | Anti-GD2 ADC M3554 in ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-10-2024-57130

M3554 for Solid Tumors · Recruiting Participants for Phase ... This study is the first to demonstrate the effectiveness of anti-GD2 antibody-drug conjugates (ADCs) in targeting solid tumors, showing significant cytotoxic ...

3. trialx.com trialx.com/clinical-trials/listings/293862/anti-gd2-adc-m3554-in-advanced-solid-tumors/?&radius=10&place=Seoul,%20etc.&user_country=Korea,%20Republic%20of

Anti-GD2 ADC M3554 in Advanced Solid Tumors Overview. The purpose of this study is to establish the recommended doses and further evaluate the safety and preliminary antitumor activity ...

4. vjoncology.com vjoncology.com/video/3gr0cfikxte-m3554-an-anti-gd2-adc-for-sarcomas-and-idh-wt-glioblastoma/

AACR 2025 | M3554, an anti-GD2 ADC, for sarcomas and IDH ... This study is a phase one study as sponsored by MAR which actually assess the clinical activity and the safety of new anti-tumor agent and ADC.

5. emdserono.com emdserono.com/us-en/company/news/press-releases/oncology-update-03-06-2024.html

2024-06-03 Innovative Oncology Pipeline of DNA Damage ... M3554 will be evaluated in patients with solid tumors with high GD2 prevalence such as neuroblastoma, where GD2 has been validated as a target ...

6. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT113/761544/Abstract-CT113-A-first-in-human-phase-1

Abstract CT113: A first-in-human phase 1, multicenter, open ... M3554 is a first-in-class, anti GD2 ADC (drug-to-antibody ratio: 8) that uses a unique linker-payload combination, utilizing a β-glucuronide linker.

7. sarcoma-patients.org sarcoma-patients.org/adc-m3552_sts/

M3554 in advanced solid tumors incl. soft-tissue sarcomas This study aims to determine the best dose of a new treatment, M3554, and to check its safety and early signs of effectiveness in treating soft tissue sarcoma ( ...