bb2121 for Multiple Myeloma

(KarMMa-3 Trial)

Not currently recruiting at 115 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Must be taking: Proteasome inhibitors, Immunomodulatory compounds

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Nonsecretory MM, CNS involvement, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment, bb2121 (also known as Idecabtagene vicleucel or Abecma), for people with multiple myeloma that recurs or resists treatment. It compares bb2121 to the standard treatments doctors typically use for this condition. Participants will be randomly assigned to one of two groups: one receiving bb2121 and the other receiving standard treatments. The trial seeks individuals who have tried two to four different treatments for multiple myeloma but still experience the disease's impact on daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that ongoing treatment with certain chronic medications, like immunosuppressants, may not be allowed. It's best to discuss your specific medications with the trial team.

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

Research has shown that bb2121, also known as idecabtagene vicleucel, has generally been well-tolerated in past studies. For example, one study found that many patients responded well to bb2121, and the side effects were manageable. Another study noted that patients experienced strong and lasting improvements, indicating the treatment's long-term effectiveness. However, like many powerful treatments, some side effects occurred, but the medical team managed these as expected.

For patients considering this clinical trial, it's important to know that earlier phases have already tested bb2121. These phases focused on ensuring the treatment's safety for people. The treatment has also shown promise in helping patients with similar conditions. Always consult with a healthcare provider to understand the potential risks and benefits. ^{1 2 3 4 5}

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

Researchers are excited about bb2121 for multiple myeloma because it uses a groundbreaking approach called CAR T-cell therapy. Unlike standard treatments that often involve a combination of drugs like daratumumab or bortezomib, bb2121 modifies a patient’s own T cells to specifically target and destroy cancer cells. This personalized approach not only offers the potential for a more targeted attack on the disease but also aims to provide lasting remission. With its unique mechanism of action, bb2121 could possibly transform the way multiple myeloma is treated by offering a more effective and durable solution.

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

Research has shown that bb2121, also known as idecabtagene vicleucel, yields promising results for people with relapsed or refractory multiple myeloma, a type of blood cancer. In earlier studies, about 84% of patients responded positively to the treatment, with 56% achieving undetectable cancer levels. On average, patients experienced 8.8 months without cancer progression. These results surpass those from traditional treatments for similar patients. In this trial, participants will receive either bb2121 or one of several standard regimens, depending on their most recent anti-myeloma treatment. Overall, bb2121 has demonstrated strong potential in treating multiple myeloma. ^{1 3 4 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Adults with relapsed and refractory multiple myeloma who have had 2-4 prior treatments, including Daratumumab, a proteasome inhibitor, and an immunomodulatory drug. They must be in good physical condition (ECOG status of 0 or 1), not pregnant or breastfeeding, willing to use contraception, and able to follow the study requirements for up to 15 years.

Inclusion Criteria

I have had 2 to 4 treatments for multiple myeloma.

I have been treated with DARA and drugs for immune and protein breakdown for 2 cycles.

I have seen improvement in my condition after at least one treatment.

Exclusion Criteria

I haven't received any new treatments in the last 2 weeks.

Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

My oxygen levels are below 92% without extra oxygen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either bb2121 CAR T cells or standard regimens based on randomization

6-8 weeks

Multiple visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Minimum of 5 years

Regular visits for monitoring and assessments

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• bb2121

Trial Overview The trial is testing bb2121 against standard regimens like Pomalidomide/Dexamethasone (DPd) and others. It's randomized: about two-thirds will receive bb2121; one-third will get standard treatment. The goal is to compare effectiveness and safety between these options.

How Is the Trial Designed?

Group I: Arm B- standard regimens as per Investigator's discretion Experimental Treatment 8 Interventions

The participants will receive one of following regimens dependent on the subject's most recent anti-myeloma treatment regimen: * Daratumumab (DARA) in combination with pomalidomide (POM) and low-dose dexamethasone (dex) (DPd) OR * DARA in combination with bortezomib (BTZ) and low-dose dex (DVd) OR * Ixazomib (IXA) in combination with lenalidomide (LEN) and low-dose dex (IRd) OR * Carfilzomib (CFZ) in combination with low-dose dexamethasone (Kd) OR * Elotuzumab (ELO) in combination with POM and low-dose dexamethasone (EPd)

Group II: Arm A - Administration of bb2121 Experimental Treatment 1 Intervention

bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy

bb2121 is already approved in United States, European Union for the following indications:

Approved in United States as Abecma for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Abecma for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

In a phase 2 study involving 140 patients with relapsed and refractory multiple myeloma, idecabtagene vicleucel (ide-cel) demonstrated a 73% overall response rate, with 33% achieving a complete response or better after treatment.

While ide-cel showed significant efficacy, it also resulted in high rates of toxic effects, including severe neutropenia (91%) and cytokine release syndrome (84%), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. Munshi, NC., Anderson, LD., Shah, N., et al.[2021]

Idecabtagene vicleucel (ide-cel) is a safe and effective CAR T cell therapy for relapsed/refractory multiple myeloma, showing low rates of severe side effects (6.5% cytokine release syndrome and 1.6% neurotoxicity) in a study of 62 patients with an 18.1-month follow-up.

The therapy achieved a high overall response rate of 75.8%, with 38.7% of patients reaching complete response, and the study identified specific T cell characteristics that correlate with longer-lasting responses, suggesting potential for optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Lin, Y., Raje, NS., Berdeja, JG., et al.[2023]

Idecabtagene vicleucel (ide-cel) is the first CAR T-cell therapy approved by the FDA for treating relapsed and refractory multiple myeloma, showing unprecedented results in clinical trials.

This therapy offers the potential for durable remissions and improved quality of life for patients who previously had limited treatment options, following just a single infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma. Anderson, LD.[2022]

In a study of 52 patients treated with idecabtagene vicleucel (ide-cel) for relapsed/refractory multiple myeloma, 65% experienced grade ≥ 3 cytopenias by day 30, indicating significant blood cell reductions, which required interventions like G-CSF and transfusions for many patients.

Infections were reported in 54% of patients, with 23% being severe; early infections were mostly bacterial, while later infections included both bacterial and viral types, highlighting the need for careful monitoring and management of infections post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. Logue, JM., Peres, LC., Hashmi, H., et al.[2022]

Idecabtagene vicleucel (ide-cel) demonstrated a high overall response rate of 84% and a complete response rate of 42% in patients with relapsed/refractory multiple myeloma, based on a retrospective analysis of 159 patients who received the therapy under standard-of-care conditions.

The safety profile was consistent with previous trials, with 83% of patients experiencing cytokine release syndrome and 19% experiencing neurotoxicity, indicating that ide-cel is effective and manageable even in a population with higher comorbidities than those in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. Hansen, DK., Sidana, S., Peres, LC., et al.[2023]

Idecabtagene vicleucel (ide-cel) significantly improved overall response rates in patients with triple-class exposed relapsed and refractory multiple myeloma, showing an odds ratio of 5.30 compared to conventional care.

Patients treated with ide-cel also experienced better progression-free survival and overall survival, with hazard ratios of 0.50 and 0.37, respectively, indicating a substantial benefit over conventional treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. Shah, N., Mojebi, A., Ayers, D., et al.[2022]

The introduction of new drug classes, including CAR-T therapy targeting BCMA, has significantly improved the 5-year survival rate of multiple myeloma patients, doubling it over the past two decades.

Idecabtagene vicleucel (ide-cel) is the first CAR-T therapy approved for treating relapse or refractory multiple myeloma, showing promising clinical efficacy and relatively lower toxicity, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel for relapsed/refractory multiple myeloma: a review of recent advances. Tu, W., Xiao, Y., Wang, Y., et al.[2022]

Patients with multiple myeloma who do not respond to existing therapies have limited survival, but new treatments like CAR T-lymphocytes, bispecific antibodies, and antibody-drug conjugates are showing promise in early trials.

Idecabtagene vicleucel (ide cel) and belantamab mafodotin (belamaf) have been approved for use in relapsed/refractory multiple myeloma based on positive results from phase 2 studies, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. Lakshman, A., Kumar, SK.[2022]

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]

Idecabtagene vicleucel, a CAR T-cell therapy targeting BCMA, showed a 72% overall response rate and a 28% complete response rate in 100 adult patients with relapsed/refractory multiple myeloma after a median follow-up of 10.7 months.

While the therapy demonstrated significant efficacy, serious adverse reactions were reported in 67% of patients, including cytokine release syndrome and neurologic toxicities, necessitating a Risk Evaluation and Mitigation Strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. Sharma, P., Kanapuru, B., George, B., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024850

Idecabtagene Vicleucel in Relapsed and Refractory ... Idecabtagene vicleucel (ide-cel, also called bb2121) showed promising efficacy in a phase 1 study involving patients with relapsed or refractory myeloma.

2. abecma.com abecma.com/is-abecma-right-for-me/abecma-results

ABECMA® Clinical Trial Results See ABECMA® (idecabtagene vicleucel) clinical trial results for adults with relapsed/refractory multiple myeloma and how they responded to treatment.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36690910/

Phase 2 results of idecabtagene vicleucel (ide-cel, bb2121 ... The overall response rate was 89% (median follow-up, 12.9 months). The best overall response was stringent complete response in 5 patients (56%), very good ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125008523

Standard-of-care idecabtagene vicleucel for relapsed/ ... The median progression-free survival (PFS) was 8.8 months. These data were superior to those seen in historical cohorts of similar patients.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19500

Outcomes of ide-cel in patients with relapsed/refractory ... The median follow-up was 11.4 months. The objective response rate was 84%; sCR was seen in 56% of patients, VGPR in 16%, PR in 12%, and PD in 16 ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2101/503044/Efficacy-and-Safety-of-Idecabtagene-Vicleucel-ide

Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in ... In cohort 2c, with a median follow-up of 27.9 months, ide-cel demonstrated deep and durable responses; complete response (CR) rate was 74.2% ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03361748

NCT03361748 | Efficacy and Safety Study of bb2121 in ... This is an open label, single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory multiple ...