bb2121 for Multiple Myeloma

(KarMMa-3 Trial)

Recruiting at 109 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

381 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM). The study is anticipated to randomize approximately 381 subjects with RRMM. Approximately 254 subjects will be randomized to Treatment Arm A and approximately 127 subjects will be randomized to Treatment Arm B.

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.

What data supports the effectiveness of the treatment idecabtagene vicleucel (ide-cel) for multiple myeloma?

Research shows that idecabtagene vicleucel (ide-cel) improves response rates, progression-free survival, and overall survival in patients with relapsed and refractory multiple myeloma compared to conventional care. It has been approved by the FDA and offers hope for more durable remissions and better quality of life for patients who have limited treatment options. ^{1 2 3 4 5}

Is idecabtagene vicleucel (bb2121) safe for humans?

Idecabtagene vicleucel (bb2121) has been studied for safety in patients with multiple myeloma. Serious side effects occurred in 67% of patients, including cytokine release syndrome (a severe immune reaction) and neurologic toxicities in 9% and 4% of patients, respectively. Some patients also experienced a condition called hemophagocytic lymphohistiocytosis/macrophage activation syndrome, with two fatalities reported. ^{1 4 6 7 8}

What makes the treatment ide-cel unique for multiple myeloma?

Idecabtagene vicleucel (ide-cel) is unique because it is a CAR T-cell therapy that targets a specific protein called B-cell maturation antigen (BCMA) on cancer cells, offering a new option for patients with multiple myeloma who have not responded to other treatments. This therapy uses the patient's own immune cells, which are modified to better recognize and attack the cancer cells, providing deep and durable responses. ^{1 3 7 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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 am 18 years old or older.

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.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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) 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, 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]

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]

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]

References

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

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. [2021]

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

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. [2022]

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

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

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

Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. [2023]

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

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. [2023]

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

FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel for relapsed/refractory multiple myeloma: a review of recent advances. [2022]

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

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