TAK-186 for Advanced Cancer

Recruiting at 47 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

97 Participants Needed

Trial Summary

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 TAK-186 (also known as MVC-101 or EGFR x CD3 COBRA) safe for humans?

The research on treatments targeting EGFRvIII, a mutation found in some cancers, shows that these therapies can be effective without causing serious side effects in animal models. However, specific safety data for TAK-186 in humans is not provided in the available research. ^{1 2 3 4 5}

Is TAK-186 (also known as MVC-101 or EGFR x CD3 COBRA) generally safe for humans?

Research on treatments targeting EGFRvIII, like TAK-186, shows promising results in targeting cancer cells without harming normal cells, suggesting a favorable safety profile. In studies, these treatments have effectively targeted tumor cells in mice without serious side effects, indicating potential safety in humans. ^{1 2 3 4 6}

How is the drug TAK-186 unique in treating advanced cancer?

TAK-186 is unique because it targets specific proteins (EGFR and EGFRvIII) that are often overexpressed in certain cancers, using a novel approach that combines a humanized antibody with a toxin to kill cancer cells more effectively. ^{1 4 7 8 9}

What makes the drug TAK-186 unique for treating advanced cancer?

TAK-186 is unique because it targets both EGFR and its mutant form EGFRvIII, which are often overexpressed in various cancers, using a novel approach that combines a humanized antibody with a diphtheria toxin fragment to specifically attack cancer cells. ^{1 4 7 8 9}

What is the purpose of this trial?

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. The drug works by targeting a specific protein on cancer cells to help stop their growth.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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 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 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]

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]

References

1. United States 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. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy. [2020]

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

Selective Targeting of Glioblastoma with EGFRvIII/EGFR Bitargeted Chimeric Antigen Receptor T Cell. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The EGFR variant III mutant as a target for immunotherapy of glioblastoma multiforme. [2023]

5. Switzerland 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice. [2022]

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

A bivalent recombinant immunotoxin with high potency against tumors with EGFR and EGFRvIII expression. [2023]

8. United States 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. [2018]

9. United States 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. [2019]