Cilta-cel + Talquetamab for Multiple Myeloma

(MonumenTAL-8 Trial)

Recruiting at 8 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Car-t, Bcma, Gprc5d, others

Disqualifiers: Prior car-t, Allogenic transplant, 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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to define the safety of Ciltacabtagene Autoleucel (Cilta-cel) and Talquetamab in participants with high-risk multiple myeloma (MM).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are in Cohort 2, you should not have taken a strong CYP450 inducer recently. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Cilta-cel + Talquetamab for Multiple Myeloma?

Ciltacabtagene autoleucel (cilta-cel) has shown strong and lasting responses in patients with multiple myeloma who have already tried many other treatments, and it has been approved by the FDA for this use. Patients have reported improvements in their quality of life after receiving this treatment. ^{1 2 3 4 5}

Is the combination of Cilta-cel and Talquetamab safe for humans?

Cilta-cel, a type of CAR T-cell therapy, has been approved for treating multiple myeloma and generally has a tolerable safety profile, with side effects that are mostly manageable. It has shown consistent safety over time, although patients may experience a range of adverse effects from mild to severe. ^{1 2 3 6 7}

What makes the treatment Cilta-cel + Talquetamab unique for multiple myeloma?

Cilta-cel is a personalized CAR T-cell therapy that targets BCMA on cancer cells, offering deep and long-lasting responses in patients with relapsed or refractory multiple myeloma, even after many other treatments have failed. It is unique because it uses the patient's own modified T-cells to attack the cancer, and it has shown better efficacy compared to similar treatments like ide-cel. ^{1 2 3 4 6}

Research Team

Janssen Research & Development, LLC Clinical trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with high-risk multiple myeloma. Participants must have had at least three prior treatments and show disease progression or lack of response to the last therapy. Newly diagnosed patients ineligible for stem cell transplant can join too. They should be fairly active (ECOG score 0-1) and women able to bear children need a negative pregnancy test.

Inclusion Criteria

I have been diagnosed with multiple myeloma and it can be measured.

* Cohorts 1 and 3: Received at least 3 prior lines of antimyeloma therapy and have undergone greater than or equal to (\>=) 1 complete cycle of the therapy. Cohort 2: Be newly diagnosed MM and considered ineligible for high-dose chemotherapy with autologous stem cell transplant (ASCT)

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants with newly diagnosed multiple myeloma undergo daratumumab, lenalidomide, and dexamethasone (DRd) induction therapy

8-12 weeks

Bridging Therapy

Participants with relapsed and/or refractory multiple myeloma receive multiple cycles of talquetamab bridging therapy

4-8 weeks

CAR-T Therapy

Participants receive Ciltacabtagene Autoleucel (Cilta-cel) therapy

1-2 weeks

Consolidation Treatment

Participants receive multiple cycles of talquetamab consolidation treatment

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years and 5 months

Treatment Details

Interventions

• Ciltacabtagene Autoleucel
• Talquetamab

Trial Overview The study tests the safety of Ciltacabtagene Autoleucel (Cilta-cel) and Talquetamab in combination with other drugs like Lenalidomide, Dexamethasone, and Daratumumab in treating high-risk multiple myeloma. It aims to find out how well these combinations work.

Participant Groups

Group I: Cohort 1:Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T) Therapy Experimental Treatment 2 Interventions

Participants with relapsed and/or refractory multiple myeloma (RRMM) will be administered Cilta-cel followed by multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first.

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

Approved in United States as Carvykti for:

• Relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody

Approved in European Union as Carvykti for:

• Relapsed and refractory multiple myeloma after one or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Ciltacabtagene autoleucel (cilta-cel) therapy significantly improved health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma, with a notable decrease in reported symptoms such as pain and fatigue from 85.2% at baseline to 22.2% by Day 184.

The majority of patients (70.8%) felt that cilta-cel met or exceeded their treatment expectations, highlighting its efficacy and the positive impact of a long treatment-free period on their overall health perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. Cohen, AD., Hari, P., Htut, M., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma, with a median progression-free survival not reached in the cilta-cel group compared to 11.8 months in the standard-care group, based on a phase 3 trial with 419 participants.

The cilta-cel group also showed higher overall response rates (84.6% vs. 67.3%) and complete response rates (73.1% vs. 21.8%) compared to standard care, although most patients experienced grade 3 or 4 adverse events, including cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. San-Miguel, J., Dhakal, B., Yong, K., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) has been approved by the FDA as a fifth-line treatment option for patients with relapsed or refractory multiple myeloma, marking a significant advancement in therapy options for this challenging condition.

Cilta-cel is notable for being the second chimeric antigen receptor T-cell therapy targeting BCMA to receive regulatory approval within a year, highlighting the rapid development of innovative treatments in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel OK'd for Multiple Myeloma. [2022]

Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, has shown deep and durable response rates in patients with multiple myeloma who have undergone multiple lines of treatment, indicating its effectiveness even in heavily pretreated cases.

The review highlights the notable adverse events associated with cilta-cel and discusses ongoing studies that may change how multiple myeloma is managed in the future, emphasizing the therapy's potential impact on treatment paradigms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel for the treatment of multiple myeloma. Holstein, SA.[2023]

Ciltacabtagene autoleucel (cilta-cel) is a CAR-T therapy for adult patients with relapsed or refractory multiple myeloma, and the estimated average healthcare costs for administering this therapy in the US are approximately $160,933 per patient over a 12-month period, excluding the cost of the therapy itself.

The analysis highlights various cost components associated with cilta-cel therapy, including apheresis, bridging therapy, and management of adverse events, which can aid healthcare decision-makers in evaluating the economic implications of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. Jagannath, S., Joseph, N., Crivera, C., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) is a CAR T-cell therapy that effectively targets B-cell maturation antigen (BCMA) in patients with relapsed or refractory multiple myeloma, showing early and long-lasting responses based on the Phase 1b/2 CARTITUDE-1 study.

While cilta-cel has a tolerable safety profile with manageable adverse effects, it generally demonstrates better efficacy compared to another CAR T-cell therapy, idecabtagene vicleucel (ide-cel), although both therapies have comparable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. Chekol Abebe, E., Yibeltal Shiferaw, M., Tadele Admasu, F., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) demonstrated a significantly higher overall response rate (84% vs. 28%) and longer progression-free survival in patients with relapsed/refractory multiple myeloma compared to standard non-CAR-T therapies, based on a comparison of 113 patients in the CARTITUDE-1 study and 190 patients from the MAMMOTH dataset.

In the modified intent-to-treat population, cilta-cel showed an even more impressive overall response rate of 96% compared to 30% in the MAMMOTH cohort, indicating its potential as a highly effective treatment option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. Costa, LJ., Lin, Y., Cornell, RF., et al.[2022]

References

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

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. [2023]

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

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]

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

Cilta-cel OK'd for Multiple Myeloma. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel for the treatment of multiple myeloma. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]

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

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. [2022]