CAR T Cell Therapy for Multiple Myeloma

(QUINTESSENTIAL Trial)

Recruiting at 100 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Must be taking: Immunomodulatory, Proteasome inhibitors

Disqualifiers: CNS involvement, Active infection, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Arlocabtagene Autoleucel (also known as BMS-986393 or CC-95266) to evaluate its effectiveness and safety for people with multiple myeloma, a type of blood cancer. The trial includes two groups, both receiving this experimental treatment. It seeks participants whose multiple myeloma has returned or did not respond after several other treatments. Participants should have noticeable symptoms and a condition that worsened after their last treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions a 'washout period' (time without taking certain medications) for some treatments before a procedure called leukapheresis. It's best to discuss your specific medications with the trial team.

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

Research has shown that Arlocabtagene Autoleucel, a treatment for multiple myeloma, has promising safety results. In earlier studies, patients generally tolerated this treatment well. Importantly, some studies found it effective and free of severe side effects for most patients. Additionally, other studies have focused on determining a safe dose, helping to ensure the treatment's general safety. However, like any treatment, some risks may remain, and individual experiences can vary. ^{1 2 3 4 5}

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

Unlike standard treatments for multiple myeloma, which often include chemotherapy or proteasome inhibitors like bortezomib, arlocabtagene autoleucel is a form of CAR T cell therapy that uses genetically engineered T cells to target and destroy cancer cells. This treatment works by harnessing the patient's own immune system to specifically attack myeloma cells, potentially leading to more precise and effective results. Researchers are excited about this approach because it offers a new mechanism of action that could provide longer-lasting remissions with fewer side effects compared to traditional therapies.

What evidence suggests that Arlocabtagene Autoleucel could be an effective treatment for multiple myeloma?

Research has shown that Arlocabtagene Autoleucel, or arlo-cel, holds promise for treating relapsed or hard-to-treat multiple myeloma. In earlier studies, 87% of patients responded well to arlo-cel, with their cancer shrinking or disappearing. Notably, 53% of patients achieved a complete response, showing no signs of cancer. Another study reported an even higher response rate of 96% after just one treatment. In this trial, participants will join different cohorts to receive arlo-cel, which could be a strong option for patients whose multiple myeloma has returned or hasn't responded to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

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 treatment. Specific details about who can join are not provided, but typically participants need to meet certain health standards and have a history of the condition being studied.

Inclusion Criteria

Participants must have measurable disease during screening

I am fully active or can carry out light work.

I have been diagnosed with multiple myeloma according to IMWG standards.

Exclusion Criteria

I haven't had treatments targeting GPRC5D or other MM treatments without the needed break before leukapheresis.

Other protocol-defined Inclusion/Exclusion criteria apply

My multiple myeloma has affected or previously affected my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Arlocabtagene Autoleucel (BMS-986393) CAR T Cell Therapy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986393

Trial Overview The study is testing BMS-986393, which is a CAR T cell therapy targeting GPRC5D, a protein often found on myeloma cells. The goal is to see how effective and safe this therapy is in treating patients whose multiple myeloma has relapsed or resisted other treatments.

How Is the Trial Designed?

Group I: Arlocabtagene Autoleucel Cohort 2 Experimental Treatment 1 Intervention

Group II: Arlocabtagene Autoleucel Cohort 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Lead Sponsor

Trials

19

Recruited

3,100+

Published Research Related to This Trial

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]

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]

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]

C-CAR088, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 96.4% in patients with relapsed or refractory multiple myeloma, with significant rates of complete response (10.7%) and stringent complete response (46.4%).

The therapy showed a favorable safety profile, with 93.5% of patients experiencing cytokine release syndrome (CRS) that was manageable and reversible, and no dose-limiting toxicities reported across the tested dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Qu, X., An, G., Sui, W., et al.[2022]

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]

Chimeric antigen receptor (CAR) T-cell therapy shows great promise for treating relapsed/refractory multiple myeloma (RRMM), building on its success in other blood cancers like acute lymphocytic leukemia and diffuse large B-cell lymphoma.

The review highlights six potential target antigens for CAR T-cell therapy in multiple myeloma and discusses the safety profiles of existing CAR T-cell treatments, indicating a significant advancement in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. Huang, H., Wu, HW., Hu, YX.[2020]

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]

In a study involving 16 patients with relapsed or refractory multiple myeloma, the bispecific CS1-BCMA CAR-T cells showed a high overall response rate of 81%, with 38% achieving a stringent complete response, indicating strong efficacy in targeting this challenging cancer.

The treatment had a manageable safety profile, with 38% of patients experiencing mild cytokine release syndrome and significant hematological adverse events, but no neurological toxicities were reported, suggesting a favorable safety outcome for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Li, C., Xu, J., Luo, W., et al.[2023]

CAR T cell therapy, originally successful for treating leukemia, is now being explored for multiple myeloma, targeting specific antigens like BCMA and CD138.

Preliminary results from clinical trials indicate that CAR T cell therapy shows promise in treating multiple myeloma, although only a limited number of patients have been treated so far.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs in the Lead Against Multiple Myeloma. Ormhøj, M., Bedoya, F., Frigault, MJ., et al.[2018]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06297226

NCT06297226 | Study of Arlocabtagene Autoleucel (BMS- ... The purpose of this study is to evaluate the effectiveness and safety of Arlocabtagene Autoleucel (BMS-986393) in participants with relapsed or refractory ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS7564

QUINTESSENTIAL-2: A phase 3 study comparing efficacy ... Following a single infusion of arlo-cel at the recommended ph2 dose (RP2D) of 150 × 106 CAR T cells, overall response rate (ORR) was 96% (23/24) ...

3. onclive.com onclive.com/view/arlo-cel-elicits-87-orr-in-heavily-pretreated-relapsed-refractory-multiple-myeloma

Arlo-cel Elicits 87% ORR in Heavily Pretreated, Relapsed ... Arlocabtagene autoleucel demonstrated an 87% overall response rate in relapsed/refractory multiple myeloma, with a 53% complete response rate in ...

4. cancernetwork.com cancernetwork.com/view/arlo-cel-yields-efficacy-safety-in-previously-treated-r-r-multiple-myeloma

Arlo-Cel Yields Efficacy, Safety in Previously Treated R/R ... As a 1-time dose, arlo-cel yielded promising efficacy and safety for patients with previously treated relapsed/refractory multiple myeloma.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06121843

NCT06121843 | A Study to Evaluate the Safety ... A Study to Evaluate the Safety, Effectiveness and Tolerable Dose of Arlocabtagene Autoleucel (BMS-986393) in Novel Combinations in Participants With ...

6. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper201356.html

Efficacy and Safety with Extended Follow-up in a Phase ... Initial data from a phase 1 study in pts with heavily pretreated RRMM suggested that a single infusion of BMS-986393 was efficacious with a favorable safety ...