TAK-280 for Advanced Cancer

Recruiting in Palo Alto (17 mi)

+23 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Takeda

Disqualifiers: Autoimmune disease, Major surgery, Active infection, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The main aim of this study is to find out the safety, tolerability, and effect of TAK- 280 in participants with unresectable, locally advanced or metastatic cancer who have experienced treatment failure or are intolerant to standard therapies. Participants will be treated with TAK-280 for up to 14 treatment cycles. Each treatment cycle will be 28 days. After the last dose of study drug, participants will be followed up for survival every 12 weeks for a total of 48 weeks.

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.

How is the treatment TAK-280 unique for advanced cancer?

TAK-280 is unique because it involves the use of gamma delta T-cells, which are a type of immune cell that can directly attack cancer cells and enhance the body's immune response against tumors. This approach is different from traditional cancer treatments as it leverages the body's own immune system to target and destroy cancer cells.

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Eligibility Criteria

This trial is for adults with advanced or metastatic cancer who haven't responded to standard treatments or can't tolerate them. They should be relatively active (with a good performance status), have measurable disease, and not have had major surgery recently. People with known allergies to TAK-280, autoimmune diseases, recent live vaccines, ongoing infections, low oxygen levels without support, or unresolved wounds are excluded.

Inclusion Criteria

I am 18 years old or older.

My cancer is advanced, cannot be surgically removed, and has spread.

My cancer can be measured by scans, except if it's prostate cancer with only bone spread.

Exclusion Criteria

I haven't had live vaccines in 4 weeks or any vaccine in 2 weeks, except the flu shot.

History of known autoimmune disease

I do not have a serious or uncontrolled infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive TAK-280 to determine the recommended doses for expansion

Up to 14 months

Visits on Days 1, 8, 15, and 22 of each 28-day cycle

Cohort-expansion

Participants receive TAK-280 at determined doses in 28-day cycles until disease progression or withdrawal

Up to 14 months

Visits on Days 1, 8, 15, and 22 of each 28-day cycle

Follow-up

Participants are monitored for survival every 12 weeks after the last dose

48 weeks

Participant Groups

The study tests the safety and effects of a new cancer drug called TAK-280 over up to 14 cycles of treatment (each cycle lasts 28 days). The goal is to see how well participants tolerate this drug and what impact it has on their cancer when other treatments have failed.

Group I: Dose-escalation Phase: TAK-280 Experimental Treatment 1 Intervention

Participants will receive TAK-280 intravenous (IV) infusion on Days 1, 8, 15, and 22 of a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal from study occurs.

Group II: Cohort-expansion Phase: TAK-280 High or low Dose Experimental Treatment 1 Intervention

Participants will receive either TAK-280 high or low dose in one selected indication and only one dose level of TAK-280 in the remaining indications as determined from the dose-escalation phase of the study in 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal from study occurs.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

SCRI Tennessee Oncology Nashville Nashville, TN

The University of Texas MD Anderson Cancer Center Houston, TX

Princess Margaret Hospital Toronto, Canada

Centre Hospitalier Universitaire de Sherbrooke CHUS Sherbrooke, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Takeda Lead Sponsor

Takeda Development Center Americas, Inc. Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours. [2021] Adoptive transfer of ex vivo expanded autologous Vγ9Vδ2 T cells may be of therapeutic benefit for cancer because of their potent direct cytotoxicity towards tumour cells, synergistic cytotoxicity when combined with aminobisphosphonates and enhancement of antibody-dependent cell-mediated cytotoxicity.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Improving the Efficiency of Vγ9Vδ2 T-Cell Immunotherapy in Cancer. [2021] Increasing immunological knowledge and advances in techniques lay the ground for more efficient and broader application of immunotherapies. gamma delta (γδ) T-cells possess multiple favorable anti-tumor characteristics, making them promising candidates to be used in cellular and combination therapies of cancer. They recognize malignant cells, infiltrate tumors, and depict strong cytotoxic and pro-inflammatory activity. Here, we focus on human Vγ9Vδ2 T-cells, the most abundant γδ T-cell subpopulation in the blood, which are able to inhibit cancer progression in various models in vitro and in vivo. For therapeutic use they can be cultured and manipulated ex vivo and in the following adoptively transferred to patients, as well as directly stimulated to propagate in vivo. In clinical studies, Vγ9Vδ2 T-cells repeatedly demonstrated a low toxicity profile but hitherto only the modest therapeutic efficacy. This review provides a comprehensive summary of established and newer strategies for the enhancement of Vγ9Vδ2 T-cell anti-tumor functions. We discuss data of studies exploring methods for the sensitization of malignant cells, the improvement of recognition mechanisms and cytotoxic activity of Vγ9Vδ2 T-cells. Main aspects are the tumor cell metabolism, antibody-dependent cell-mediated cytotoxicity, antibody constructs, as well as activating and inhibitory receptors like NKG2D and immune checkpoint molecules. Several concepts show promising results in vitro, now awaiting translation to in vivo models and clinical studies. Given the array of research and encouraging findings in this area, this review aims at optimizing future investigations, specifically targeting the unanswered questions.

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

Activation of cytotoxic T lymphocytes by self-differentiated myeloid-derived dendritic cells for killing breast cancer cells expressing folate receptor alpha protein. [2022] Adoptive cell transfer (ACT) is a promising approach for cancer treatment. Activation of T lymphocytes by self-differentiated myeloid-derived antigen-presenting-cells reactive against tumor (SmartDC) resulted in specific anti-cancer function. Folate receptor alpha (FRα) is highly expressed in breast cancer (BC) cells and thus potential to be a target antigen for ACT. To explore the SmartDC technology for treatment of BC, we create SmartDC expressing FRα antigen (SmartDC-FRα) for activation of FRα-specific T lymphocytes. Human primary monocytes were transduced with lentiviruses containing tri-cistronic complementary DNA sequences encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and FRα to generate SmartDC-FRα. Autologous T lymphocytes were activated by SmartDC-FRα by coculture. The activated T lymphocytes exhibited enhanced cytotoxicity against FRα-expressing BC cell cultures. Up to 84.9 ± 6.2% of MDA-MB-231 and 89.7 ± 1.9% of MCF-7 BC cell lines were specifically lysed at an effector-to-target ratio of 20:1. The cytotoxicity of T lymphocytes activated by SmartDC-FRα was also demonstrated in three-dimensional (3D) spheroid culture of FRα-expressing BC cells marked by size reduction and spheroid disruption. This study thus portray the potential development of T lymphocytes activated by SmartDC-FRα as ACT in FRα-expressing BC treatment.

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

Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. [2021] E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B and human interleukin-2. It shares an amino acid sequence with denileukin diftitox, but has improved purity and an increased percentage of active monomer. We undertook a multicenter, single-arm phase II study of E7777 in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) to evaluate its efficacy, safety, pharmacokinetics, and immunogenicity. A total of 37 patients were enrolled, of which 17 and 19 patients had PTCL and CTCL, respectively, and one patient with another type of lymphoma (extranodal natural killer/T-cell lymphoma, nasal type), diagnosed by the Central Pathological Diagnosis Committee. Among the 36 patients with PTCL and CTCL, objective response rate based on the independent review was 36% (41% and 31%, respectively). The median progression-free survival was 3.1 months (2.1 months in PTCL and 4.2 months in CTCL). The common adverse events (AEs) observed were increased aspartate aminotransferase (AST) / alanine aminotransferase (ALT), hypoalbuminemia, lymphopenia, and pyrexia. Our results indicated that a 9 µg/kg/d dose of E7777 shows efficacy and a manageable safety profile in Japanese patients with relapsed or refractory PTCL and CTCL, with clinical activity observed across the range of CD25 expression. The common AEs were manageable, but increase in ALT / AST, hypoalbuminemia, and capillary leak syndrome should be carefully managed during the treatment.

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

Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses. [2023] Recombinant immunotoxins have been shown to cure human tumor xenografts in mice, but their biodistribution to both tumors and normal organs has not been reported. Anti-Tac(Fv)-PE38 is a single-chain recombinant immunotoxin composed of the variable heavy and light domains of the anti-Tac monoclonal antibody that reacts with the primate interleukin 2 (IL2) receptor alpha subunit (IL2R alpha or CD25) fused to a truncated form of Pseudomonas exotoxin (PE). 125I-labeled anti-Tac(Fv)-PE38 was given i.v. to immunodeficient mice each bearing two A431 tumors, one that expresses IL2R alpha (ATAC-4) and one that does not (A431, parental). A single i.v. dose of 4 microg/mouse caused complete regression of the IL2R alpha + tumor. At 6 h, over 6% of the injected dose/g was found in the ATAC-4 tumor, and 2% was in the A431 tumor. Uptake in the ATAC-4 tumor was higher than in any other tissue. Sections of tumor examined by autoradiography indicated that anti-Tac(Fv)-PE38 was distributed throughout the entire tumor, with some portions having higher uptake than others. By subtracting uptake in tumors without receptor (A431) from uptake in receptor-containing tumors (ATAC-4), we calculated that at least 400 molecules/cell specifically bound to IL2R alpha-positive tumor cells at 90 min and 750 molecules/cell bound at 360 min. This is similar to the 400-870 molecules/cell required for >99.9% killing of ATAC-4 cells growing as a monolayer. The results show that solid tumors in mice can be eradicated like cells in tissue culture, and that delivery of less than 1000 molecules/cell is sufficient to cause complete tumor regressions.