TAK-079 for Multiple Myeloma

Not currently recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Takeda

Must be taking: Antimyeloma therapy

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B/C, Amyloidosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAK-079 for individuals with newly diagnosed multiple myeloma, a type of blood cancer. The trial aims to determine the best dose for future studies when TAK-079 is combined with standard treatments like lenalidomide (a cancer drug) and dexamethasone (a steroid). Those recently diagnosed with multiple myeloma who have not yet received treatment might be suitable candidates. The trial will also assess the safety of TAK-079 for participants continuing from a previous study. As a Phase 1 trial, this research focuses on understanding 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 protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently in another interventional study or have had certain treatments like radiation therapy or major surgery recently.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TAK-079 is generally safe and well-tolerated. In earlier studies, participants taking TAK-079 experienced few side effects. The treatment led to long-lasting reductions in certain cells, such as plasmablasts and NK cells, which play a role in multiple myeloma. Another study found that TAK-079 was safe and effective for patients with a difficult-to-treat type of multiple myeloma. These findings suggest that TAK-079 could be a promising option, with evidence supporting its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TAK-079 for multiple myeloma because it introduces a unique mechanism of action by targeting CD38, a protein highly expressed on myeloma cells, which is different from traditional therapies like proteasome inhibitors or immunomodulatory drugs. This targeted approach could potentially offer better precision in attacking cancer cells while sparing healthy ones. Additionally, TAK-079 is administered subcutaneously, which can be more convenient and less invasive compared to intravenous treatments. By combining it with established drugs like lenalidomide and dexamethasone, TAK-079 aims to enhance overall treatment effectiveness and provide new hope for patients with this challenging condition.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that TAK-079 holds promise for treating multiple myeloma, a type of blood cancer. In this trial, participants may receive TAK-079 combined with lenalidomide and dexamethasone (LenDex). One study found that this combination led to 67% of patients with relapsed or hard-to-treat multiple myeloma experiencing some improvement. TAK-079 is a medicine that helps the immune system find and destroy cancer cells. Another group in this trial will receive TAK-079 combined with bortezomib, lenalidomide, and dexamethasone (VRd), which has been shown to help patients live longer. Early results are encouraging, but more research is needed to confirm long-term benefits. ^{2 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed Multiple Myeloma who have measurable disease, can take blood clot prevention meds if on lenalidomide, and have a life expectancy over 3 months. They must not have had prior MM therapy (except certain cases), recent major surgery or radiation, other clinical trials within 4 weeks, severe allergies to study drugs, active infections or certain other cancers.

Inclusion Criteria

I can take blood thinners while on lenalidomide as advised.

I can take care of myself but might not be able to do heavy physical work.

I have multiple myeloma needing treatment, as per IMWG criteria, and haven't been treated yet.

Exclusion Criteria

Your heart's electrical activity, as shown on a test called an ECG, should not have a specific measurement (QTcF) higher than 470 milliseconds. If the machine shows a higher value, a qualified person should double-check it on another test.

I haven't needed strong antibiotics for a serious infection in the last 14 days.

I am not allergic to the medication TAK-079 or its components.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAK-079 in combination with LenDex or VRd. TAK-079 is administered subcutaneously once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter.

Up to 2 years

Safety Extension

Participants who have previously received and tolerated TAK-079-based parent study will continue to the extension study to evaluate the long-term safety profile of TAK-079.

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAK-079

Trial Overview The trial tests the safety and optimal dose of TAK-079 combined with standard myeloma treatments like Lenalidomide and Dexamethasone. It also offers continued access to TAK-079 for those previously in related studies and assesses long-term safety.

How Is the Trial Designed?

Group I: Treatment Phase: TAK-079 and VRd Experimental Treatment 5 Interventions

TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are \>75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.

Group II: Treatment Phase: TAK-079 and LenDex Experimental Treatment 4 Interventions

TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are greater than (\>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.

Group III: Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex) Experimental Treatment 5 Interventions

TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study.

Who Is Running the Clinical Trial?

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

Monoclonal antibodies like daratumumab and elotuzumab, especially when combined with other treatments, have shown high response rates and improved survival in patients with relapsed and refractory multiple myeloma, highlighting their efficacy in targeting specific plasma cell proteins.

CAR T cell therapy, particularly targeting B-cell maturation antigen (BCMA), has demonstrated dramatic remissions in patients with difficult-to-treat multiple myeloma, although it can lead to significant side effects like cytokine release syndrome and neurotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic Malignancies: Plasma Cell Disorders. Dhodapkar, MV., Borrello, I., Cohen, AD., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03439280

NCT03439280 | A Study to Investigate the Safety, ... TAK-079 is being tested to treat people who have relapsed and/or refractory multiple myeloma (RRMM). This study will assess the safety, tolerability, efficacy, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6589825/

Novel agents in multiple myeloma - PMC Isatuximab, in combination with lenalidomide/dexamethasone has been evaluated in a phase 1b clinical trial in 57 R/R MM patients. The overall response rate was ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468294221001647

Immunotherapy in multiple myeloma Daratumumab, Lenalidomide, and dexamethasone was approved for transplant ineligible newly diagnosed multiple myeloma (NDMM) [15], and Daratumumab ...

4. ashpublications.org ashpublications.org/bloodneoplasia/article/1/4/100043/517909/Phase-1b-study-of-the-anti-CD38-antibody

Phase 1b study of the anti-CD38 antibody mezagitamab in ... In a phase 1b study of relapsed/refractory myeloma, the anti-CD38 antibody mezagitamab was well tolerated and showed preliminary activity.

5. researchgate.net researchgate.net/publication/341632755_A_phase_Ib_study_of_TAK-079_an_investigational_anti-CD38_monoclonal_antibody_mAb_in_patients_with_relapsed_refractory_multiple_myeloma_RRMM_Preliminary_results

A phase Ib study of TAK-079, an investigational anti-CD38 ... The clinical benefit rate (minimal response or better) in all 12 patients enrolled at the RP2 dose was 67%. At a median follow-up of 7.5 months, PFS not ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7319013/

Safety, tolerability, pharmacokinetics and ... TAK‐079 was well tolerated and s.c. administration elicited more durable reductions in plasmablasts and NK cells. This plasmacytolytic profile could be useful ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.8539

A phase Ib study of TAK-079, an investigational anti-CD38 ... TAK-079 monotherapy is safe, generally well tolerated, and active in patients with RRMM through tested doses. Clinical activity occurred early and was durable.

8. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/140/426135/Preliminary-Results-from-a-Phase-1b-Study-of-TAK

Preliminary Results from a Phase 1b Study of TAK-079, an ... TAK-079 was safe and well-tolerated in a first in human study in healthy subjects with potent pharmacodynamic activity when administered as a SC ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2950328024000438

Phase 1b study of the anti-CD38 antibody mezagitamab in ... In a phase 1b study of relapsed/refractory myeloma, the anti-CD38 antibody mezagitamab was well tolerated and showed preliminary activity.