Zevor-cel for Multiple Myeloma

Not currently recruiting at 13 trial locations

Overseen By Nishan Rajakumaraswamy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Carsgen Therapeutics, Ltd.

Must be taking: Proteasome inhibitors, IMiDs, CD38 antibodies

Must not be taking: Steroids, Anti-cancer treatments

Disqualifiers: HIV, Hepatitis, Active infection, others

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

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 Zevor-cel for individuals with multiple myeloma, a type of blood cancer that often recurs after treatment. The study tests a therapy using engineered T cells, a type of immune cell, that target a protein called BCMA found on cancer cells. It seeks participants who have tried various treatments for their myeloma but no longer see results. Ideal candidates have undergone prior treatments, including specific drugs, and still have measurable disease. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that you cannot have received any anti-cancer treatment, steroids, or live vaccines before certain procedures in the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Zevor-cel is likely to be safe for humans?

Research has shown that zevor-cel, a therapy using modified immune cells to target the BCMA protein, has promising safety results. In one study with patients who had previously tried multiple treatments for multiple myeloma, participants responded well to zevor-cel for over three years.

Although all treatments can cause side effects, zevor-cel has generally been well-tolerated, with most patients not experiencing serious side effects. It is important to note that zevor-cel remains under study, and researchers continue to gather more safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for multiple myeloma, which often includes chemotherapy, immunotherapy, and stem cell transplants, Zevor-cel (CT053) acts on a different principle by using CAR-BCMA T cells. These engineered T cells are designed to specifically target and destroy cancer cells that express the BCMA protein, a hallmark of multiple myeloma. Researchers are excited about Zevor-cel because this targeted approach could potentially lead to more effective treatment with fewer side effects, offering new hope for patients who have not responded to traditional therapies.

What evidence suggests that Zevor-cel might be an effective treatment for multiple myeloma?

Research has shown that Zevor-cel, a type of CAR T-cell therapy, targets a protein called BCMA on multiple myeloma cells. This method shows promise in treating multiple myeloma that has returned or hasn't responded to standard treatments. In this trial, participants will receive Zevor-cel, which studies have found to lead to significant improvements in many patients, with some even reaching remission, meaning the cancer is under control or not detectable. However, about half of the patients may experience a return of the cancer over time. This therapy is effective for many, but like all treatments, it doesn't work for everyone and can produce varying results. ^{1 2 4 6 7}

Who Is on the Research Team?

Shaji Kumar, MD

Principal Investigator

Mayo

Are You a Good Fit for This Trial?

This trial is for adults aged 18-79 with relapsed/refractory multiple myeloma who've had specific prior treatments and are not responding to their last therapy. They must have good organ function, no recent major surgery or cancer treatments, no active infections like HIV/HBV/HCV, and agree to use contraception for a year post-treatment.

Inclusion Criteria

I am fully active or can carry out light work.

Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 12 months after T cell infusion

My blood, kidney, and liver tests are within normal ranges.

Exclusion Criteria

I am unable or unwilling to follow the clinical trial requirements.

I still have side effects from past treatments that haven't gone away.

I have taken steroids before my cell collection or before reducing my white blood cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Enrolled subjects undergo leukapheresis to collect autologous mononuclear cells for manufacture of investigational drug product (zevor-cel)

4 weeks

Lymphodepletion and Treatment

Subjects receive lymphodepletion prior to zevor-cel infusion

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Long-term Follow-up

All subjects who complete the study, as well as those who withdraw after receiving zevor-cel, will undergo a 15-year long-term follow-up study

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Zevor-cel (CT053)

Trial Overview The study tests Zevor-cel (CT053), a CAR T-cell therapy targeting BCMA in patients whose multiple myeloma has returned or resisted treatment. It's an early-stage trial assessing the safety and effectiveness of this new intervention.

How Is the Trial Designed?

Group I: CAR-BCMA T Cells Experimental Treatment 1 Intervention

Phase 1b will include a dose escalation followed by an expansion cohort to determine the recommended dose for the expansion part. After recommended Phase 2 is determined, patients in Phase 2 will be treated.

Who Is Running the Clinical Trial?

Carsgen Therapeutics, Ltd.

Lead Sponsor

Trials

8

Recruited

640+

CARsgen Therapeutics Co., Ltd.

Lead Sponsor

Trials

33

Recruited

3,100+

Published Research Related to This Trial

Carfilzomib shows significant efficacy in treating multiple myeloma, with a 28% complete response rate and a 93% overall response rate among 2,487 patients analyzed across 12 clinical trials.

While carfilzomib improves survival rates (93% progression-free survival at 1 year), it is associated with a higher incidence of cardiotoxicity compared to traditional treatments, although it does not significantly increase the risk of peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Carfilzomib in the Treatment of Multiple Myeloma：A Systematic Evaluation]. Luo, T., Xia, HL.[2020]

In a phase 3 trial with 386 patients suffering from relapsed and refractory multiple myeloma, idecabtagene vicleucel (ide-cel) significantly improved progression-free survival (13.3 months) compared to standard treatments (4.4 months), indicating its efficacy in this challenging patient population.

The treatment with ide-cel resulted in a 71% overall response rate, including a 39% complete response rate, although it was associated with high rates of adverse events (93% grade 3 or 4), including cytokine release syndrome in 88% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. Rodriguez-Otero, P., Ailawadhi, S., Arnulf, B., et al.[2023]

Recent advancements in multiple myeloma treatment have introduced several new drugs that significantly improve patient outcomes, each with unique mechanisms of action and side effect profiles.

The review emphasizes the importance of monitoring and managing specific adverse events associated with these new treatments, providing practical guidance for healthcare providers to enhance patient safety and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Ludwig, H., Delforge, M., Facon, T., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) is a CAR T-cell therapy that effectively targets B-cell maturation antigen (BCMA) in patients with relapsed or refractory multiple myeloma, showing early and long-lasting responses based on the Phase 1b/2 CARTITUDE-1 study.

While cilta-cel has a tolerable safety profile with manageable adverse effects, it generally demonstrates better efficacy compared to another CAR T-cell therapy, idecabtagene vicleucel (ide-cel), although both therapies have comparable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. Chekol Abebe, E., Yibeltal Shiferaw, M., Tadele Admasu, F., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03915184

NCT03915184 | Clinical Trial to Evaluate Zevor-cel (CT053 ... This is an open label, multi-center, phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous chimeric antigen receptor-B-cell maturation ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482220/

Phase II study of zevorcabtagene autoleucel, a fully human ... While CAR T-cell therapies have improved outcomes in RRMM in many parts of the world, their benefit to Chinese patients has been limited due to ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4762/532827/Subgroup-Analyses-of-Phase-2-Study-Evaluating-the

Subgroup Analyses of Phase 2 Study: Evaluating the Efficacy ... Evaluating the efficacy of fully human BCMA-targeting CAR T cells (Zevorcabtagene Autoleucel) in patients with relapsed/refractory multiple myeloma.

4. carsgen.com carsgen.com/en/news/20231212/

CARsgen Presents Updated Research Results on Zevor-cel Zevor-cel (CT053) is a fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. The New Drug Application (NDA) for ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1650568/full

Long-term follow-up of patients with relapsed/refractory ... Despite the remarkable short-term efficacy of BCMA CAR-T-cell therapy, approximately 50% of patients experience relapse or disease progression during long-term ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4845/505634/Three-Year-Follow-up-on-Efficacy-and-Safety

Three-Year Follow-up on Efficacy and Safety Results from ... At approximately 3 years of follow-up, heavily pre-treated RRMM patients maintained deep and durable responses after receiving a single infusion of zevor-cel.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123114467

Three-Year Follow-up on Efficacy and Safety Results from ... At approximately 3 years of follow-up, heavily pre-treated RRMM patients maintained deep and durable responses after receiving a single infusion of zevor-cel.