TAK-186 for Advanced Cancer

Not currently recruiting at 52 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Maverick Therapeutics, Inc

Must not be taking: Immune-suppressive drugs, Corticosteroids

Disqualifiers: Autoimmune disease, Cardiovascular disease, Gastrointestinal disorders, others

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

Compensation: Varies

Number of Visits: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment, TAK-186 (also known as MVC-101 or EGFR x CD3 COBRA), for individuals with advanced or hard-to-remove cancers, such as certain lung, colon, and head and neck cancers. The main goal is to assess patient tolerance and cancer response to the treatment. It is suitable for those whose cancer has returned or progressed after treatments like chemotherapy or targeted therapy. Participants will receive the treatment weekly and undergo regular monitoring for side effects and changes in their cancer. 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 therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like cytotoxic chemotherapy, monoclonal antibodies, and some other therapies must be stopped within specific timeframes before starting the trial. It's best to discuss your current medications with the trial team to understand any specific requirements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like cytotoxic chemotherapy, monoclonal antibodies, and some other therapies must be stopped within specific timeframes before starting the trial. It's best to discuss your current medications with the trial team to understand any specific requirements.

Is there any evidence suggesting that TAK-186 is likely to be safe for humans?

Research shows that TAK-186 (also known as MVC-101) is under study to assess its safety and tolerability in people with advanced cancers, particularly when surgery isn't an option. Earlier studies suggest that TAK-186 aids the immune system in attacking cancer cells, showing promising results in tumor reduction.

The current research primarily aims to identify any side effects and evaluate the treatment's tolerability. Detailed information on specific side effects is not yet available. As the treatment is in early testing stages, it holds potential, but its full safety profile is still under development. This phase typically focuses on determining the right dosage and identifying any negative effects.

For those considering trial participation, it's important to know that safety remains a top priority, and any new treatment undergoes thorough testing before becoming widely available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment options for advanced cancers like non-small cell lung cancer, which often include chemotherapy, targeted therapy, and immunotherapy, TAK-186 works differently by specifically targeting tumor-associated antigens. This unique mechanism of action allows TAK-186 to home in on cancer cells more precisely, potentially reducing damage to healthy tissues. Researchers are excited about TAK-186 because it combines this targeted approach with a novel infusion method, which could lead to more consistent and controlled delivery of the treatment. This innovative strategy has the potential to improve outcomes and minimize side effects compared to existing therapies.

What evidence suggests that TAK-186 might be an effective treatment for advanced cancer?

Research has shown that TAK-186, which participants in this trial may receive, may help fight certain cancers. Studies have found that it can guide T cells, a type of immune cell, to attack cancer cells with a specific marker, sometimes leading to smaller solid tumors. This trial includes a Dose Escalation Phase and a Cohort Expansion Phase, focusing on safety and effectiveness. While the main focus of current studies is to check safety, these early findings suggest that TAK-186 might help treat advanced cancers that cannot be removed by surgery. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with advanced or metastatic cancer that can't be removed, who have a life expectancy of at least 12 weeks and measurable disease. They must be in relatively good health (ECOG ≤1), have acceptable blood test results, and provide informed consent. Specific types of cancers like NSCLC, HNSCC, and CRC are included if they've progressed after standard treatments.

Inclusion Criteria

Life expectancy ≥ 12 weeks

Archival Tissue: Participants must allow acquisition of existing formalin-fixed paraffin-embedded (FFPE) archival tumor sample, either a block or unstained slides.

My cancer can be measured by scans and hasn't been treated with radiation in the area to be measured.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive TAK-186 infusion with dose escalation in sequential cohorts

Up to 13 months

Weekly infusions

Cohort Expansion

Further characterization of safety and anti-tumor activity in specific cancer cohorts

Up to 13 months

Weekly infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Visits at 30 days, 90 days, and every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAK-186

Trial Overview The trial is testing TAK-186 (MVC-101) for safety and effectiveness in treating various advanced cancers. Participants will receive the treatment for up to 13 months with follow-ups at specified intervals to monitor their response.

How Is the Trial Designed?

Group I: Dose Escalation Phase Experimental Treatment 1 Intervention

TAK-186 initial 60 minutes infusion and 30 minutes subsequent infusions on Day 1 of every week in Dose Escalation Phase. Participants may receive additional treatment with TAK-186. Dose escalation will be carried out in sequential cohorts of escalating doses.

Group II: Cohort Expansion Phase: NSCLC Experimental Treatment 1 Intervention

Participants with non-small cell lung cancer (NSCLC) will be randomized to receive low dose or high dose of RDE of TAK-186 infusion on Day 1 of every week during Dose Expansion Phase of the study. Participants may receive additional treatment with TAK-186. Based on the results for this cohort additional cohorts for HNSCC and CRC, may be enrolled.

Who Is Running the Clinical Trial?

Maverick Therapeutics, Inc

Lead Sponsor

Trials

1

Recruited

100+

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

The study successfully developed CAR-T cells targeting the EGFRvIII mutation, which is present in about 10% of non-small cell lung cancer cases, demonstrating their ability to specifically recognize and kill cancer cells in laboratory tests.

In mouse models, these EGFRvIII-CAR-T cells not only inhibited the spread of lung cancer cells but also significantly improved survival rates without causing serious side effects, suggesting a promising therapeutic approach for lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy. Zhang, Z., Jiang, J., Wu, X., et al.[2020]

The bivalent recombinant immunotoxin DT390-BiscFv806 shows high cytotoxicity against glioblastoma cells and head and neck squamous cell carcinoma, with IC50 values indicating it is particularly effective against cells expressing EGFRvIII, being 4 orders of magnitude more potent against these cells than against non-expressing cells.

In animal studies, DT390-BiscFv806 significantly inhibited tumor growth in models with U87-EGFRvIII and U87 tumors, achieving growth inhibition rates of 76.3% and 59.4%, respectively, suggesting its potential as a targeted cancer therapy for tumors with high EGFR expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A bivalent recombinant immunotoxin with high potency against tumors with EGFR and EGFRvIII expression. Meng, J., Liu, Y., Gao, S., et al.[2023]

The 3C10 monoclonal antibody (mAb) specifically targets the type III mutant epidermal growth factor receptor (EGFRvIII) found in certain gliomas, showing significant accumulation in tumor tissues in a study involving athymic nude mice with glioma xenografts.

The study demonstrated that 3C10 mAb has a high tumor-to-blood ratio, indicating its potential as both a diagnostic and therapeutic agent for gliomas expressing EGFRvIII, with detectable tumor localization as early as 3 hours post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor. Takasu, S., Takahashi, T., Okamoto, S., et al.[2019]

The study developed a new transgenic mouse model that expresses a murinized CAR targeting EGFRvIII, which is effective in producing high-quality CAR-transduced T cells for glioblastoma research.

Infusing these CAR T cells into glioma-bearing mice significantly prolonged survival, especially when combined with an anti-EP4 compound, suggesting a promising approach for enhancing immunotherapy effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice. Chuntova, P., Hou, Y., Naka, R., et al.[2022]

The study identifies EGFRvIII, a tumor-specific antigen found in about 30% of glioblastomas, as a promising target for immunotherapy, particularly in glioma stem cells (GSCs) which better represent the tumor than traditional cell lines.

CAR-engineered T cells targeting EGFRvIII showed the ability to specifically recognize and kill glioblastoma cells without affecting normal cells, indicating a potential for safe and effective treatment options for patients with this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Morgan, RA., Johnson, LA., Davis, JL., et al.[2022]

The M27-derived CAR T cells specifically target both EGFRvIII and wild-type EGFR on tumor cells while sparing normal cells, demonstrating effective tumor lysis without causing toxicity to healthy tissues.

In mouse models, the M27-28BBZ CAR T cells significantly inhibited the growth of glioblastoma tumors and prolonged survival, suggesting that this targeted approach could be a promising treatment for patients with EGFR/EGFRvIII-overexpressing glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Targeting of Glioblastoma with EGFRvIII/EGFR Bitargeted Chimeric Antigen Receptor T Cell. Jiang, H., Gao, H., Kong, J., et al.[2019]

EGFRvIII, a common mutation in high-grade gliomas like glioblastoma multiforme, leads to a receptor that promotes tumor cell survival and is resistant to standard EGFR inhibitors, making it a critical target for therapy.

Targeting EGFRvIII with specific monoclonal antibodies and vaccines, such as the CDX-110 peptide vaccine, has shown promise in preclinical and clinical studies, offering a potential new approach to treat GBM and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EGFR variant III mutant as a target for immunotherapy of glioblastoma multiforme. Chistiakov, DA., Chekhonin, IV., Chekhonin, VP.[2023]

The study demonstrates that a bispecific antibody (Vγ2 x PD-L1) effectively redirects Vγ2Vδ2 T cells to target and eliminate PD-L1 positive tumor cells, enhancing their activation and anti-tumor response.

Combining this bispecific antibody with adoptive transfer of Vγ2Vδ2 T cells significantly inhibits tumor growth in xenograft models, suggesting a promising strategy for improving the efficacy of T cell therapies against PD-L1 expressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell. Yang, R., He, Q., Zhou, H., et al.[2022]

The monoclonal antibody mAb 806 significantly reduced tumor volume and increased survival in mice with gliomas expressing high levels of the mutant DeltaEGFR, demonstrating its efficacy as a potential treatment for aggressive gliomas.

Mechanistically, mAb 806 treatment led to decreased tumor growth and angiogenesis, increased apoptosis, and reduced phosphorylation of DeltaEGFR, indicating its role in targeting the active form of the receptor and promoting cancer cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth suppression of intracranial xenografted glioblastomas overexpressing mutant epidermal growth factor receptors by systemic administration of monoclonal antibody (mAb) 806, a novel monoclonal antibody directed to the receptor. Mishima, K., Johns, TG., Luwor, RB., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04844073

NCT04844073 | A Study of TAK-186 (Also Known as MVC- ... The main aim of this study is to check for side effects and tolerability of TAK-186 (also known as MVC-101) in adults with unremovable advanced or ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04844073

TAK-186 (Also Known as MVC-101) in Adults With Advanced ... The main aim of this study is to check for side effects and tolerability of TAK-186 (also known as MVC-101) in adults with unremovable advanced or metastatic ...

3. withpower.com withpower.com/trial/phase-2-carcinoma-2-2021-64e6b

TAK-186 for Advanced Cancer · Info for Participants This trial is testing a new drug called TAK-186 to see if it is safe and effective for adults with advanced cancers that cannot be removed by surgery.

4. clinicaltrials.takeda.com clinicaltrials.takeda.com/study-detail/74eb6adc7d334623?idFilter=%5B%22CP-MVC-101-01%22%5D

A Study of TAK-186 (Also Known as MVC-101) in Adults ... The main aim of this study is to check for side effects and tolerability of TAK-186 (also known as MVC-101) in adults with unremovable advanced or metastatic ...

5. jitc.bmj.com jitc.bmj.com/content/10/6/e004336

Regression of EGFR positive established solid tumors in ... TAK-186 shows potent redirected T cell killing of antigen expressing tumor cells. In vivo efficacy studies demonstrate regressions of established solid tumors.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7049494/

New data highlighting the efficacy and safety outcomes ... Osimertinib was effective in the treatment of NSCLC patients with rare EGFR mutations and that the toxicities caused by the treatment were acceptable.