CAR T-Cell Therapy for Multiple Myeloma

Overseen By Oliver Kong, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nanjing IASO Biotechnology Co., Ltd.

Must not be taking: Monoclonal antibodies, Cytotoxic chemotherapy

Disqualifiers: GVHD, Severe heart disease, 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 tests a new treatment called CT103A, a type of CAR T-cell therapy, for individuals with multiple myeloma that is resistant to treatment or has recurred. The main goal is to determine the safety and effectiveness of CT103A. The trial seeks participants who have tried at least three different treatments for multiple myeloma and have experienced disease progression. Participants should also have specific protein levels in their blood or urine that are easily measurable. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop monoclonal antibodies 21 days before, cytotoxic chemotherapy or proteasome inhibitors 14 days before, and immunomodulators 7 days before apheresis. Glucocorticoids over 20 mg/day must be stopped 7 days before apheresis, but some steroids are allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CT103A, a type of CAR T-cell therapy made entirely from human cells, is generally safe for patients with relapsed or hard-to-treat multiple myeloma. Studies have found that CT103A remains safe over time, even in patients who have undergone many previous treatments. Long-term research indicates that side effects are manageable, with no new or unexpected problems occurring. This suggests that the treatment is relatively safe for patients, even those with extensive prior treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which often include chemotherapy, immunomodulatory drugs, and proteasome inhibitors, CT103A is a fully human BCMA chimeric antigen receptor (CAR) T-cell therapy. This therapy is unique because it involves reprogramming a patient's own T-cells to specifically target and attack cancer cells expressing the BCMA protein, which is commonly found in multiple myeloma. Researchers are excited about CT103A because it offers a tailored, potentially more effective approach with the ability to directly engage the patient's immune system, promising improved outcomes for those who have relapsed or are resistant to other treatments.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma?

Research has shown that CT103A, a therapy using specially modified immune cells, yields promising results for treating relapsed or hard-to-treat multiple myeloma. In studies, 33% to 88% of patients experienced tumor reduction or remission. Long-term follow-up indicates that CT103A's benefits persist, with the treatment remaining active in the body over time. Additionally, research suggests this therapy can extend patients' lives and is generally safe. These findings offer hope for those with difficult-to-treat multiple myeloma. ^{2 5 6 7 8}

Who Is on the Research Team?

Nanjing IASO Biotherapeutics Co.,Ltd. Clinical trial

Principal Investigator

Nanjing IASO Biotechnology Co., Ltd.

Are You a Good Fit for This Trial?

Adults with relapsed/refractory multiple myeloma who have measurable lesions, an ECOG score of 0 or 1, and agree to use contraception. They must have tried at least three prior therapies including a proteasome inhibitor, immunomodulator, and anti-CD38 therapy. Excluded are those with certain severe diseases, recent major surgery or other clinical trial participation within the last month.

Inclusion Criteria

You have specific levels of proteins in your blood or urine that show the presence of the disease.

The subject must personally sign an informed consent form approved by the ethics committee in writing

My myeloma worsened within 12 months after my last treatment, excluding CAR-T therapy.

Exclusion Criteria

I do not have severe liver, kidney, or metabolic diseases needing treatment.

You have active hepatitis B or C, HIV, or other serious infections.

I have had an organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Collection of peripheral blood mononuclear cells from participants

1 week

Bridging therapy

Optional therapy administered at the discretion of the investigator

Lymphodepleting chemotherapy

Participants receive chemotherapy to deplete lymphocytes before infusion

1 week

CT103A infusion

Single infusion of CT103A administered to participants

Day 0

28-Day safety evaluation period

Participants are monitored for safety following the infusion

4 weeks

Post-treatment follow-up

Participants are monitored for safety and efficacy until disease progression or other endpoints

Up to 2 years

Long-term follow-up

Participants enter a long-term follow-up under a separate protocol for at least 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Fully human BCMA chimeric antigen receptor autologous T cell injection (CT103A)

Trial Overview The study is testing CT103A - a type of CAR-T cell therapy targeting BCMA on cancer cells in patients whose multiple myeloma has returned after treatment or didn't respond to previous treatments. It's an open-label phase Ib trial focusing on safety and effectiveness.

How Is the Trial Designed?

Group I: CT103A in patients with RRMM Experimental Treatment 1 Intervention

After lymphodepletion, CT103A will be administered as a single infusion.

Who Is Running the Clinical Trial?

Nanjing IASO Biotechnology Co., Ltd.

Lead Sponsor

Trials

10

Recruited

690+

Nanjing IASO Biotherapeutics Co.,Ltd

Lead Sponsor

Trials

7

Recruited

360+

Published Research Related to This Trial

In a phase I clinical trial involving 30 multiple myeloma patients, anti-BCMA CAR T cells showed favorable safety with no high-grade cytokine release syndrome and only one case of low-grade neurologic toxicity.

The treatment demonstrated significant efficacy, with 10 out of 15 patients with measurable disease achieving a partial response or better, and 4 patients converting to minimal residual disease-negative complete response, indicating strong antimyeloma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. Garfall, AL., Cohen, AD., Susanibar-Adaniya, SP., et al.[2023]

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]

BCMA CAR T-cell therapy has shown impressive response rates of 60% to 100% in patients with relapsed/refractory myeloma, indicating its potential as a highly effective treatment option.

While the therapy can lead to severe but reversible toxicities like cytokine release syndrome and neurotoxicity, ongoing studies aim to enhance its safety and efficacy through combinations with other treatments and gene editing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. Cohen, AD.[2019]

B-cell maturation antigen (BCMA) CAR T cells are emerging as a highly effective treatment for multiple myeloma, showing promise for inclusion in first-line therapy based on clinical and preclinical data.

Advancements in patient stratification through genomic analysis and improvements in CAR T-cell manufacturing are enhancing early diagnosis, management of side effects, and overall access to this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? Rasche, L., Hudecek, M., Einsele, H.[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]

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]

In a study of 21 patients with relapsed and refractory multiple myeloma treated with BCMA-chimeric antigen receptor T cells (CART), 17 patients showed effective responses, including 10 achieving complete remission, indicating a promising efficacy of this treatment.

The treatment was associated with manageable adverse reactions, primarily cytokine release syndrome (CRS), which occurred in 20 patients but was mostly mild (Grade 1 or 2), demonstrating that BCMA-CART can be safely administered with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma]. Zhang, XY., Ding, HY., Gang, DX., et al.[2022]

Chimeric antigen receptor T cells targeting the BCMA protein show promise as a potent treatment for multiple myeloma, based on preliminary results from an ongoing phase I clinical trial in China.

The therapy was well tolerated by patients and led to complete and durable responses in those with relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sending CAR T Cells After Multiple Myeloma. [2018]

CAR T-cell therapy targeting B-cell maturation antigen (BCMA) has shown promising results in treating multiple myeloma, with high-quality responses observed in heavily pretreated patients, and ongoing Phase 3 trials are comparing its efficacy against standard treatments.

While CAR T-cell therapy can lead to sustained responses in some patients, most eventually relapse due to factors like loss of CAR T cells or antigen expression, prompting research into improving CAR design and safety measures, such as suicide gene systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for multiple myeloma: state of the art and prospects. van de Donk, NWCJ., Usmani, SZ., Yong, K.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05698303?term=IASO&rank=10

A Study of Fully Human BCMA Chimeric Antigen Receptor ... A Study of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (CT103A) in the Treatment of Patients With Relapsed/​Refractory Multiple ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525001624007408

Long-term safety and efficacy of the fully human CAR-T ... Long-term follow-up demonstrated that CT103A confers durable clinical benefit for RRMM patients based on the sustained presence of fully human CAR-T cells.

3. ashpublications.org ashpublications.org/blood/article/137/21/2890/475033/A-phase-1-study-of-a-novel-fully-human-BCMA

A phase 1 study of a novel fully human BCMA-targeting CAR ... Results from previously published clinical trials showed that ∼33% to 88% of patients with relapsed/refractory MM (RRMM) had objective ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11021094/

Exploring the efficacy and safety of anti-BCMA chimeric ... Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes.

5. iasobio.com iasobio.com/phone/info.php?id=30

Clinical trial results of the BCMA CAR-T Co-developed by ... A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39520053/

Long-term safety and efficacy of the fully human CAR-T ... This study presents the updated safety and efficacy profiles of CT103A in patients with relapsed/refractory multiple myeloma (RRMM) after long-term follow-up.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8025

CT103A, a novel fully human BCMA-targeting CAR-T cells ... CT103A, which is designed with a fully human BCMA-specific CAR structure, has shown sustained efficacy and durable safety in heavily pretreated relapsed and ...

8. journals.lww.com journals.lww.com/hemasphere/fulltext/2022/06003/s187__updated_phase_1_2_data_of_safety_and.88.aspx

updated phase 1/2 data of safety and efficacy of ct103a, ... CT103A, a fully human BCMA-directed CAR-T therapy, showed excellent safety and promising efficacy in the ongoing phase 1/2 FUMANBA-1 study.