CYAD-211 Immunotherapy for Multiple Myeloma

(IMMUNICY-1 Trial)

Not currently recruiting at 6 trial locations

Overseen By Celyad Oncology Medical Monitor, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celyad Oncology SA

Must not be taking: Investigational agents, BCMA-targeted therapy

Disqualifiers: CNS tumor, Recent stem cell transplant, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called CYAD-211, a type of immunotherapy, for individuals with multiple myeloma, a blood cancer that has returned or resisted other treatments. The main goal is to determine the safety and effectiveness of CYAD-211 after patients receive specific chemotherapy drugs to prepare their bodies. Suitable candidates have already tried at least two different treatments for multiple myeloma, including drugs known as IMiD and PIs, without success. As a Phase 1 trial, this research aims to understand how CYAD-211 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 requires that you stop any prior systemic therapy for multiple myeloma at least 14 days before starting the preconditioning chemotherapy.

Is there any evidence suggesting that CYAD-211 is likely to be safe for humans?

Research has shown that CYAD-211 is safe for people with relapsed or refractory multiple myeloma, a type of blood cancer. Studies have found that patients tolerate the treatment well, with no major safety issues. Importantly, little evidence of graft-versus-host disease (GvHD), where donor cells attack the patient's body, has been observed. Data from different dose levels support these findings, indicating that CYAD-211 is generally safe for humans. Overall, early results suggest that this treatment is well-tolerated and safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which typically involve chemotherapy, stem cell transplants, and targeted therapies, CYAD-211 offers a fresh approach by using CAR-T cell therapy. This treatment is unique because it involves genetically modifying T-cells, a type of immune cell, to better recognize and attack cancer cells. CYAD-211 is designed to enhance the immune system's ability to fight multiple myeloma, potentially offering a more targeted and personalized attack on the cancer cells. Researchers are excited because this method could lead to more effective treatments with fewer side effects compared to traditional options.

What evidence suggests that CYAD-211 might be an effective treatment for multiple myeloma?

Research has shown that CYAD-211, a type of cell therapy, has potential in treating multiple myeloma, a type of blood cancer. In earlier studies, some patients experienced a partial response, indicating improvement in their condition. Additionally, five patients maintained stable disease, meaning their cancer did not worsen. The treatment demonstrated that patients could go an average of 18.3 months without disease progression, suggesting it can help control the cancer for a significant period. Although almost all patients experienced some immune-related side effects, these were generally manageable. This evidence suggests CYAD-211 could be a valuable option for those whose multiple myeloma has returned or not responded to other treatments. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma that has come back or hasn't responded to at least two treatments, including IMiD and PIs. Participants must have measurable disease, be in decent physical shape (ECOG ≤2), and have good organ function. They can't join if they've had recent cancer treatment, CNS tumor involvement, a stem cell transplant too close to the study start date, or no response to previous BCMA-targeted therapy.

Inclusion Criteria

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

My multiple myeloma has not responded to at least two treatments, including IMiD and PIs.

My blood, kidney, liver, lung, and heart functions are all within normal ranges.

Exclusion Criteria

I have had BCMA-targeted therapy without significant improvement.

I have or had a brain tumor that affects my health.

I had my own stem cell transplant less than 3 months ago or a donor's within the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconditioning Chemotherapy

Participants receive a non-myeloablative preconditioning chemotherapy regimen with fludarabine and/or cyclophosphamide

1-2 weeks

Treatment

Participants receive an infusion of CYAD-211 (anti-BCMA CAR-T) cells

Up to 36 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CYAD-211

Trial Overview The IMMUNICY-1 study is testing CYAD-211's safety and effectiveness after patients receive lymphodepletion drugs Fludara (fludarabine) and/or Endoxan (cyclophosphamide). It aims to understand how this new therapy behaves in the body of those with relapsed/refractory multiple myeloma.

How Is the Trial Designed?

Group I: CYAD-211 Experimental Treatment 3 Interventions

Infusion post preconditioning non-myeloablative chemotherapy

Who Is Running the Clinical Trial?

Celyad Oncology SA

Lead Sponsor

Trials

13

Recruited

1,300+

Published Research Related to This Trial

Anti-CD38 monoclonal antibodies have become a standard treatment for multiple myeloma, significantly enhancing patient response when used alongside traditional therapies.

New therapies targeting BCMA, including drug conjugates and bispecific T-cell engagers, show promise as effective options for treating multiple myeloma, particularly in patients who have become resistant to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies as an addition to current myeloma therapy strategies. Jullien, M., Touzeau, C., Moreau, P.[2021]

In a phase 1 study of 33 patients with relapsed or refractory multiple myeloma, the CAR T-cell therapy bb2121 demonstrated a high objective response rate of 85%, with 45% of patients achieving complete responses.

While bb2121 showed promising antitumor activity, it also had significant safety concerns, with 76% of patients experiencing cytokine release syndrome and 42% experiencing neurological toxic effects, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. Raje, N., Berdeja, J., Lin, Y., et al.[2021]

Novel agents like immunomodulatory drugs (IMiDs) and proteasome inhibitors (such as bortezomib) have significantly improved treatment outcomes for myeloma, showing better responses when used in combination with steroids and chemotherapy.

These therapies, initially used for relapsed or refractory myeloma, are now being tested in newly diagnosed patients, leading to higher response rates and longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for multiple myeloma. Dingli, D., Rajkumar, SV.[2009]

In a phase II trial involving 69 patients with relapsed or refractory multiple myeloma, the combination of anti-BCMA and anti-CD19 CAR T cells resulted in a high overall response rate of 92%, with 60% achieving a complete response.

The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine release syndrome, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. Wang, Y., Cao, J., Gu, W., et al.[2022]

T-cell redirecting bispecific antibodies and CAR T cells are effective treatments for multiple myeloma but are associated with significant adverse events, including cytokine release syndrome and neurotoxicity.

The European Myeloma Network recommends specific management strategies for these adverse events, such as premedication, corticosteroids, and monitoring for symptoms, to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Ludwig, H., Terpos, E., van de Donk, N., et al.[2023]

HBI0101, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 75% in a phase I study involving 20 heavily pre-treated patients with relapsed/refractory multiple myeloma, with a dose-dependent increase in efficacy observed in higher doses.

The therapy showed a manageable safety profile, with 90% of patients experiencing only mild cytokine release syndrome and no severe toxicities, indicating that HBI0101 could be a safe and effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Asherie, N., Kfir-Erenfeld, S., Avni, B., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04613557

Safety, Activity and Cell Kinetics of CYAD-211 in Patients ... This study aims to determine the recommended dose of the allogeneic CYAD-211 (anti-BCMA CAR-T) cells after a non-myeloablative preconditioning chemotherapy in ...

2. celyad.com celyad.com/wp-content/uploads/2021/12/Celyad-Oncology_ASH2021_poster2817_IMMUNICY1_AlHomsi_final.pdf.pdf

IMMUNICY-1: Targeting BCMA with CYAD-211 to Establish ... IMMUNICY-1 is an ongoing open-label multi-center Phase 1 trial (NCT04613557) designed to evaluate CYAD-211 in adult patients with refractory or relapsed ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S000649712104756X

Immunicy-1: Targeting BCMA with Cyad-211 to Establish ... Two patients achieved partial response at dose-levels 1 and 2 while 5 patients had stable disease (SD). One patient with an ongoing SD (3 months ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-plasma-cell-10-2020-b35e4

CYAD-211 Immunotherapy for Multiple Myeloma ... The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine ...

5. onclive.com onclive.com/view/emerging-allogeneic-car-t-candidates-usher-in-a-new-era

Emerging Allogeneic CAR T Candidates Usher in a New Era Investigators are assessing the safety, clinical activity, and cell kinetics of CYAD-211 following 3 consecutive days of preconditioning with ...

6. celyad.com celyad.com/2025/02/18/celyad-oncology-announces-the-publication-of-the-preclinical-and-clinical-data-of-cyad-211-providing-proof-of-concept-of-its-mirna-based-shrna-platform/

Celyad Oncology announces the publication of ... Importantly, data highlighted an overall good safety profile and some clinical responses, with no signs of graft-versus-host disease (GvHD), ...

7. cgtlive.com cgtlive.com/view/cyad-211-induces-favorable-safety-supports-proof-of-concept-in-patients-with-relapsed-refractory-myeloma

CYAD-211 Induces Favorable Safety, Supports Proof of ... CYAD-211 demonstrated a favorable safety profile across 3 dose levels, with limited observations of graft-versus-host disease (GvHD) in adult ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT04613557

Safety, Activity and Cell Kinetics of CYAD-211 in Patients ... There were no safety concerns leading to this decision and all patients previously treated with CYAD-211 will continue to receive their protocol-defined follow- ...