Zevor-cel for Multiple Myeloma

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

105 Participants Needed

Trial Summary

What is the purpose of this trial?

A phase 1b/2, open label, multi-center, Clinical Study of Chimeric Antigen Receptor T Cells targeting BCMA in patients with relapsed and or refractory multiple myeloma.

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.

What data supports the effectiveness of the treatment Zevor-cel (CT053) for Multiple Myeloma?

Research on similar treatments like cilta-cel and ide-cel, which are also CAR-T therapies targeting BCMA, shows high response rates and improved survival in patients with multiple myeloma who have tried other treatments. These therapies have shown promising results, suggesting that Zevor-cel might also be effective. ^{1 2 3 4 5}

What safety information is available for Zevor-cel (CT053) in humans?

Cilta-cel, a similar CAR T-cell therapy, has been shown to have a tolerable safety profile in patients with multiple myeloma, with adverse effects ranging from mild to life-threatening but mostly manageable. The safety profile remains consistent over longer follow-up periods. ^{1 3 6 7 8}

Research Team

Shaji Kumar, MD

Principal Investigator

Mayo

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Cilta-cel, a BCMA-targeting CAR-T therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating the Therapeutic Potential of Idecabtagene Vicleucel in the Treatment of Multiple Myeloma: Evidence to Date. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice. [2023]

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

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy. [2023]

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

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Carfilzomib in the Treatment of Multiple Myeloma：A Systematic Evaluation]. [2020]