FT576 for Multiple Myeloma

Not currently recruiting at 18 trial locations

Overseen By Fate Trial Disclosure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fate Therapeutics

Must not be taking: Immunosuppressants, Antiepileptics

Disqualifiers: Cardiovascular disease, CNS disease, Infections, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called FT576, either alone or with daratumumab (a monoclonal antibody therapy), to evaluate its effectiveness for people with multiple myeloma, a type of blood cancer that has returned or did not respond to previous treatments. The study aims to determine the optimal dose of FT576 and assess its effectiveness both alone and in combination with daratumumab. Suitable candidates for this trial have multiple myeloma that has returned or progressed after two or more previous treatments, including specific therapies. As a Phase 1 trial, the research focuses on understanding 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, there are washout periods (time without taking certain medications) for some therapies, like chemotherapy and biologic therapy, before starting the trial treatment.

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

Research has shown that FT576 is still undergoing testing to determine its safety and tolerability. Current studies aim to identify the optimal dose for future research. Presently, information about side effects and patient responses to the treatment remains limited.

When combined with daratumumab, a drug already used for treating multiple myeloma, additional factors come into play. Daratumumab is known to benefit patients with this type of cancer but can cause side effects, particularly those related to blood. Since daratumumab is approved for another condition, its safety profile is well understood.

In summary, while daratumumab has a known safety record, the safety of FT576, especially when used alone, is still being explored in these early studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about FT576 for multiple myeloma because it uses genetically engineered natural killer (NK) cells to target and destroy cancer cells. Unlike standard treatments like chemotherapy and proteasome inhibitors, FT576 is designed to enhance the body's immune response against cancer. Additionally, when combined with daratumumab, an antibody that targets a specific protein on myeloma cells, FT576 has the potential to boost effectiveness by precisely attacking cancer cells, potentially leading to improved outcomes for patients with this challenging condition.

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

Research has shown that FT576, one of the treatments in this trial, has potential in treating multiple myeloma when used alone. In early studies, one patient who had tried five other treatments experienced significant improvement after receiving FT576. In this trial, some participants will receive FT576 alone, while others will receive FT576 combined with daratumumab. Preclinical studies found that this combination controlled tumors more effectively than either treatment alone. Daratumumab is already known to help multiple myeloma patients live longer without their cancer worsening. These findings suggest that both FT576 alone and the FT576-daratumumab combination could be effective options for treating multiple myeloma. ^{1 2 3 6 7}

Who Is on the Research Team?

Fate Trial Disclosure

Principal Investigator

Fate Therapeutics, Inc

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory Multiple Myeloma who have tried at least two or three prior therapies, depending on the regimen. They should not be severely ill (ECOG PS <2), have significant infections like HIV/HBV/HCV, recent live vaccines, organ transplants, other cancers within 2 years (with exceptions), and must meet certain blood and organ function criteria.

Inclusion Criteria

I have previously received BCMA CAR T-cell therapy or BCMA-targeted treatments.

I have relapsed or refractory multiple myeloma with measurable indicators.

My multiple myeloma has worsened after 3 treatments including IMiD, proteasome inhibitor, and anti-CD38.

Exclusion Criteria

Your white blood cell count is too low without growth factor support, or your platelet count is too low without a recent platelet transfusion.

I haven't had any cancer other than my current one in the last 2 years.

I haven't had certain cancer treatments recently before starting the FT576 trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive escalating doses of FT576 as monotherapy or in combination with daratumumab to determine the optimal dose

Varies

Expansion

Participants receive the determined optimal dose of FT576 as monotherapy or in combination with daratumumab to further evaluate safety and efficacy

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Long-term follow-up

Participants are monitored for long-term outcomes such as progression-free survival and overall survival

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Daratumumab
• Fludarabine
• FT576

Trial Overview The study tests FT576 alone and with daratumumab in different doses to find the safest and most effective amount for treating Multiple Myeloma. It's a Phase I trial that starts by increasing doses (dose-escalation) then gives it to more people at the best dose found (expansion stage).

How Is the Trial Designed?

Group I: Regimens B-B4 Experimental Treatment 5 Interventions

FT576 single dose in combination with daratumumab in subjects with r/r MM

Group II: Regimens A-A4 Experimental Treatment 4 Interventions

FT576 single dose monotherapy in subjects with r/r MM

Group III: Regimen B1 Experimental Treatment 5 Interventions

FT576 multiple dose in combination with daratumumab in subjects with r/r MM

Group IV: Regimen A1 Experimental Treatment 4 Interventions

FT576 multiple dose monotherapy in subjects with r/r MM

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

Fate Therapeutics

Lead Sponsor

Trials

22

Recruited

1,200+

Published Research Related to This Trial

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

Daratumumab received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Citations

1. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4586/492309/Interim-Phase-I-Clinical-Data-of-FT576-As

Interim Phase I Clinical Data of FT576 As Monotherapy and in ... In preclinical studies, FT576 combined with the anti-CD38 mAb daratumumab demonstrated highly effective tumor control compared to either ...

2. fatetherapeutics.com fatetherapeutics.com/wp-content/uploads/2022/12/2004-FT57676.pdf

FT576-101 Phase I Study In preclinical studies, FT576 combined with the anti-CD38 mAb daratumumab demonstrated highly effective tumor control compared to either treatment alone or to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05182073

Study Details | FT576 in Subjects With Multiple Myeloma This is a Phase I dose-finding study of FT576 as monotherapy and in combination with the monoclonal antibody daratumumab in multiple myeloma (MM).

4. aacrjournals.org aacrjournals.org/cancerres/article/81/13_Supplement/1550/667450/Abstract-1550-FT576-path-to-first-of-kind-clinical

Abstract 1550: FT576 path to first-of-kind clinical trial ... The treatment of MM-bearing mice with both FT576 and daratumumab produced greater myeloma control than either agent alone, demonstrating ...

5. researchgate.net researchgate.net/publication/365827345_Interim_Phase_I_Clinical_Data_of_FT576_As_Monotherapy_and_in_Combination_with_Daratumumab_in_Subjects_with_RelapsedRefractory_Multiple_Myeloma

Interim Phase I Clinical Data of FT576 As Monotherapy and ... Notably, one patient who had previously undergone five lines of treatment achieved a very good partial response after the second administration of FT576 ...

6. ir.fatetherapeutics.com ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-ipsc-derived-shelf-car-nk-cell

Fate Therapeutics Highlights iPSC-derived, Off-the-shelf CAR ... The multi-center Phase 1 clinical trial of FT576 is designed to assess its safety and clinical activity in adult patients with r/r MM, and to ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05182073?term=NCT05182073&rank=1

Study Details | FT576 in Subjects With Multiple Myeloma Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...