CAR-T Cell Therapy for Multiple Myeloma

No longer recruiting at 16 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Chemotherapy, Antineoplastics, Immunotherapies, others

Disqualifiers: Genetically modified cells, HSCT, 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 PHE885, a type of CAR-T cell therapy, for multiple myeloma, a type of blood cancer. The goal is to determine if this treatment is safe and effective in reducing cancer. The trial has two parts: one for patients whose cancer has returned or not responded to other treatments, and another for those newly diagnosed who have received some initial treatment. Individuals with multiple myeloma who have tried at least two different treatments, or who are newly diagnosed and have started treatment, might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy or any anti-cancer therapies (except for specific trial-related chemotherapy) at least 2 weeks before apheresis (a procedure to collect blood cells). Additionally, you must stop taking certain antibodies or immunotherapies 3 to 4 weeks before apheresis.

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

Research has shown that PHE885, a type of CAR-T cell therapy, has been tested for safety in people with multiple myeloma, a kind of blood cancer. In these studies, PHE885 demonstrated high response rates, indicating effectiveness for many participants. Importantly, no unexpected safety issues emerged, suggesting that PHE885 is generally well-tolerated, even in patients with hard-to-treat forms of the disease. While these results are promising, it is important to remember that this information comes from early research. More studies are needed to confirm these findings and ensure the treatment's safety for everyone. ^{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, PHE885 is a CAR-T cell therapy that offers a different approach. This treatment reprograms a patient’s own T-cells to specifically target and destroy multiple myeloma cells. Researchers are excited about PHE885 because it has the potential to provide a highly personalized and powerful option that directly attacks cancer cells, possibly leading to longer-lasting remissions. Additionally, this type of therapy can be effective in patients who have relapsed or are resistant to conventional treatments, offering hope where other treatments may have failed.

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

Research has shown that PHE885, a type of CAR-T cell therapy, holds promise for treating multiple myeloma, a type of blood cancer. In studies, PHE885 targets a protein called BCMA on cancer cells, aiding in their destruction. Participants in this trial will receive PHE885, including both newly diagnosed multiple myeloma patients and those with relapsed and/or refractory multiple myeloma. Specifically, some patients in these trials showed significant improvements, with many having no detectable cancer afterward. This suggests that PHE885 can effectively reduce or eliminate multiple myeloma in some patients. While more research is needed, these early results offer encouragement for those considering this treatment. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with Multiple Myeloma who've had at least two prior treatments, including specific drugs like IMiDs and proteasome inhibitors. They should have a performance status of 0 or 1 if previously treated, or up to 2 if newly diagnosed after standard therapy. Participants must not have had any genetic cell therapies before, nor certain cancer treatments close to joining the study.

Inclusion Criteria

You have a condition that can be measured according to the study's guidelines.

My blood test results are within normal ranges.

My leukapheresis material is approved for use.

Exclusion Criteria

I have previously received a genetic cell therapy but not BCMA-directed bi-specific antibodies or ADC.

I haven't had chemotherapy or other cancer treatments except for LD chemotherapy in the last 2 weeks.

I have had my own stem cell transplant within the last 6 weeks or have never had a stem cell transplant from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Relapsed and/or refractory multiple myeloma patients receive PHE885 to study safety and tolerability

28 days

Multiple visits for monitoring and dose administration

Dose Evaluation (Part B)

Newly diagnosed multiple myeloma patients receive PHE885 to study safety and tolerability

28 days

Multiple visits for monitoring and dose administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits for response assessment and monitoring

What Are the Treatments Tested in This Trial?

Interventions

• PHE885

Trial Overview The trial tests PHE885, a new type of CAR-T cell therapy targeting BCMA on myeloma cells. It's a first-in-human study assessing how safe it is and its initial effectiveness against multiple myeloma as a single agent treatment.

How Is the Trial Designed?

Group I: PHE885 (Part B) Experimental Treatment 1 Intervention

Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.

Group II: PHE885 (Part A) Experimental Treatment 1 Intervention

Relapsed and/or refractory multiple myeloma (r/r MM) patients will receive PHE885.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

The introduction of second-generation proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has significantly improved survival rates for multiple myeloma patients, but many still relapse, highlighting the need for new therapies.

B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy shows promise as a new treatment option for patients with multiple myeloma who are resistant to current standard therapies, offering a different mechanism of action to combat the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. Rodríguez-Otero, P., Prósper, F., Alfonso, A., et al.[2023]

Multiple myeloma remains an incurable disease, and patients often experience relapses after standard treatments, leading to a poor prognosis.

Chimeric antigen receptor (CAR) T-cell therapy shows promise in improving outcomes for relapsed multiple myeloma, although it is not yet approved for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells for Multiple Myeloma: The Journey So Far-And the Road Ahead. Cowan, AJ., Tuazon, SA., Portuguese, AJ., et al.[2022]

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]

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]

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 five patients with relapsed multiple myeloma receiving anti-BCMA CAR-T cell therapy, four achieved complete remission within one month, indicating strong efficacy of this treatment.

The levels of soluble BCMA (sBCMA) in plasma decreased significantly after CAR-T infusion, suggesting that sBCMA could serve as a useful biomarker for monitoring treatment response in multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma. Seipel, K., Porret, N., Wiedemann, G., 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]

CAR T-cell therapy, specifically BCMA-directed products like idecabtagene vicleucel and ciltacabtagene autoleucel, has been FDA-approved for treating relapsed/refractory multiple myeloma, showing high response rates in patients who have undergone extensive prior treatments.

Despite their effectiveness, these therapies are associated with significant immune-related side effects and relapse rates, highlighting the need for ongoing research to enhance their efficacy and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review. Sadek, NL., Costa, BA., Nath, K., et al.[2023]

In a study of 22 patients with relapsed or refractory multiple myeloma, a combination of anti-BCMA and anti-CD38 CAR-T cell therapy showed a high overall response rate of 90.9%, with over half achieving a complete response.

While the treatment demonstrated significant efficacy, it also resulted in cytokine release syndrome in 72.7% of patients, indicating the need for careful monitoring of side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. Zhang, H., Liu, M., Xiao, X., et al.[2022]

Chimeric antigen receptor (CAR)-modified T cell therapy has shown promising efficacy in treating refractory or relapsed multiple myeloma (MM) in both preclinical and clinical studies, indicating a potential new treatment avenue for this incurable disease.

The toxicities associated with CAR-T cell therapy are manageable, suggesting that this innovative approach could be a safe option for patients with MM, especially as research continues to identify effective targets and improve technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapies for multiple myeloma. Wu, C., Zhang, L., Brockman, QR., et al.[2020]

The dual-CAR T-cell therapy targeting CD138 and CD38 showed a significant anti-multiple myeloma response, resulting in a median survival of 97 days in treated mice compared to 31 days in the control group, indicating its potential efficacy.

This approach demonstrated increased specificity for cancer cells coexpressing both antigens while minimizing off-target effects on healthy tissues, suggesting a safer treatment option for multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity. Globerson Levin, A., Rawet Slobodkin, M., Waks, T., et al.[2021]

Chimeric antigen receptor (CAR)-T cell therapy shows promising efficacy and manageable toxicity in heavily pretreated multiple myeloma patients, with over 50 ongoing clinical trials exploring various CAR-T designs and targets.

The most effective CAR-T therapy so far targets B cell maturation antigen, but challenges remain, including the duration of response and the risk of prolonged cytopenia, necessitating further research to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of CAR-T cell therapies for multiple myeloma. Gagelmann, N., Riecken, K., Wolschke, C., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430604/

PHASE I STUDY DATA UPDATE OF PHE885, A FULLY ... This multicenter, open-label study (NCT04318327) characterizes the safety and efficacy of PHE885 manufactured using the novel T-Charge TM platform.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8004

Updated phase I study results of PHE885, a T-Charge ... Results: As of December 22, 2022, 46 pts received PHE885 at the following doses: 2.5e6 (n=4), 5e6 (n=13), 10e6 (n=20), 14.3e6 (n=1), and 20e6 (n ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05172596

Study Details | NCT05172596 | PHE885 CAR-T Therapy in ... This is a Phase II study to determine the efficacy and safety of PHE885, a BCMA-directed CAR-T cell therapy, manufactured with a new process. The CAR-T cell ...

4. nature.com nature.com/articles/s41408-024-01191-8

CAR-T cell therapy in Multiple Myeloma: current status and ... Seventy-six percent of Cilta-cel-treated patients developed CRS, 4.5% had ICANS and 9% had cranial nerve (CN) palsy [31]. The FDA subsequently ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11101341/

CAR T therapies in multiple myeloma: unleashing the future In addition, a remarkable CR rate of 73% was observed in this subgroup, indicating a substantial and durable treatment response. Even more ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121057815

Phase I Study of PHE885, a Fully Human BCMA-Directed ... PHE885 is a unique and fully human BCMA CAR-T cell product manufactured using the novel T-Charge TM platform, which reduces ex vivo culture time to about 24 ...