Talquetamab + Daratumumab/Pomalidomide for Multiple Myeloma

(MonumenTAL-3 Trial)

Recruiting at 265 trial locations

Overseen By Mel McMahon

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Anti-CD38 antibodies, Pomalidomide

Disqualifiers: CNS involvement, Plasma cell leukemia, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Variable (until progression or other criteria)

810 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to compare the efficacy of talquetamab subcutaneous(ly) (SC) in combination with daratumumab SC and pomalidomide (Tal-DP) and talquetamab SC in combination with daratumumab SC (Tal-D), respectively, with daratumumab SC in combination with pomalidomide and dexamethasone (DPd).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Talquetamab + Daratumumab/Pomalidomide for Multiple Myeloma?

Research shows that combining daratumumab with pomalidomide and dexamethasone improves progression-free survival in patients with multiple myeloma compared to using pomalidomide and dexamethasone alone. Additionally, daratumumab has been effective in various combinations for treating multiple myeloma, enhancing response rates and prolonging survival. ^{1 2 3 4 5}

Is the combination of Talquetamab, Daratumumab, and Pomalidomide safe for humans?

The APOLLO trial showed that the combination of Daratumumab, Pomalidomide, and Dexamethasone was generally safe for patients with multiple myeloma, with updated safety results confirming this. Daratumumab is widely used and generally safe, although not all patients respond well to it. ^{6 7 8 9 10}

What makes the Talquetamab + Daratumumab/Pomalidomide drug unique for multiple myeloma?

This treatment combines talquetamab, a novel drug, with daratumumab, pomalidomide, and dexamethasone, offering a new approach for patients with multiple myeloma who have been heavily pretreated. The combination aims to improve progression-free survival by leveraging the unique mechanisms of each component, such as daratumumab's targeting of CD38 on myeloma cells and pomalidomide's immunomodulatory effects. ^{1 2 3 11 12}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with Multiple Myeloma that has come back or didn't respond to treatment. They must have had at least one prior therapy including specific drugs, be relatively fit (ECOG score of 0-2), and have measurable disease. People can't join if they have brain involvement, severe allergies to drug components, high recent steroid use, certain other blood disorders, or their cancer doesn’t respond to similar treatments.

Inclusion Criteria

My cancer has worsened after my last treatment, as confirmed by my doctor.

My condition is officially diagnosed as multiple myeloma.

I've had treatment for myeloma that included a proteasome inhibitor and lenalidomide.

Exclusion Criteria

I have taken less than 140 mg of steroids like prednisone in the last 2 weeks.

I have been treated with pomalidomide before.

I am not allergic or intolerant to the ingredients of the study drug.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talquetamab, daratumumab, pomalidomide, and dexamethasone until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study

Variable (until progression or other criteria)

Follow-up

Participants are monitored for safety and effectiveness after treatment until death, withdrawal of consent, loss to follow-up, or end of the study

Up to 6 years 6 months

Treatment Details

Interventions

• Daratumumab
• Dexamethasone
• Pomalidomide
• Talquetamab

Trial Overview The study tests Talquetamab combined with Daratumumab and Pomalidomide (Tal-DP) or just Talquetamab and Daratumumab (Tal-D), against a known combo of Daratumumab with Pomalidomide and Dexamethasone (DPd). It aims to see which mix works best for treating Multiple Myeloma.

Participant Groups

Group I: Arm C: Talquetamab SC in Combination With Daratumumab SC (Tal-D) Experimental Treatment 3 Interventions

Participants will receive talquetamab and daratumumab as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

Group II: Arm B: Daratumumab in Combination With Pomalidomide and Dexamethasone (DPd) Experimental Treatment 3 Interventions

Participants will receive daratumumab as SC injection; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

Group III: Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and Pomalidomide (Tal-DP) Experimental Treatment 4 Interventions

Participants will receive talquetamab and daratumumab as SC injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

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

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

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

In a phase 3 trial involving 304 patients with relapsed or refractory multiple myeloma, the combination of daratumumab with pomalidomide and dexamethasone significantly improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median of 12.4 months versus 6.9 months.

While the combination treatment was effective, it was associated with a higher incidence of grade 3 or 4 adverse events, particularly neutropenia, indicating that while daratumumab enhances treatment efficacy, it may also increase the risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Dimopoulos, MA., Terpos, E., Boccadoro, M., et al.[2021]

Daratumumab significantly improves overall survival (OS) compared to pomalidomide plus low-dose dexamethasone in patients with heavily pretreated multiple myeloma, with hazard ratios indicating a strong treatment benefit (0.56 and 0.51 for two different studies).

The survival advantage of daratumumab is even more pronounced in patients who have not previously been treated with pomalidomide, suggesting it may be particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. Van Sanden, S., Ito, T., Diels, J., et al.[2019]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant anti-myeloma activity through various mechanisms, including direct apoptosis and immune system modulation, making it a key treatment for relapsed-refractory multiple myeloma (RRMM).

Clinical trials, such as CASTOR and POLLUX, demonstrated that daratumumab in combination with other therapies (like bortezomib and lenalidomide) significantly improves overall response rates and progression-free survival compared to standard treatments, leading to its approval and integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. Offidani, M., Corvatta, L., Morè, S., et al.[2021]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

In the APOLLO trial involving 304 patients with relapsed or refractory multiple myeloma, the combination of daratumumab, pomalidomide, and dexamethasone showed a median overall survival of 34.4 months compared to 23.7 months for pomalidomide and dexamethasone alone, although this difference was not statistically significant.

The safety profile indicated that serious treatment-emergent adverse events were more common in the daratumumab group (54%) compared to the pomalidomide and dexamethasone group (40%), but the overall findings support the continued use of daratumumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trial. Dimopoulos, MA., Terpos, E., Boccadoro, M., et al.[2023]

In a study of 324 relapsed/refractory multiple myeloma patients treated with daratumumab, the combination of daratumumab with lenalidomide and dexamethasone (DLd) showed a longer time-to-next-treatment (TTNT) associated with higher monocyte and white blood cell counts, as well as lower β2 microglobulin levels.

A scoring model based on monocyte counts, white blood cell counts, and β2 microglobulin levels was developed to predict durable responses to the DLd regimen, with patients scoring 0 having significantly better survival outcomes compared to those with higher scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide. Shimazu, Y., Kanda, J., Kaneko, H., et al.[2022]

Darolutamide is an FDA-approved nonsteroidal androgen inhibitor specifically for treating castration-resistant non-metastatic prostate cancer, providing a new option for patients whose PSA levels are rising despite low testosterone.

When used alongside androgen deprivation therapy (ADT), darolutamide, like other newer agents in its class, has been shown to prolong metastasis-free survival and median survival, making it an effective treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. Hamilton, J.[2021]

The document serves as a comprehensive guide to recent clinical trials involving a wide range of drugs, highlighting their potential applications in various medical conditions.

It includes detailed information on numerous drugs, such as 3,4-DAP, alemtuzumab, and imatinib mesylate, which are currently being studied for their efficacy and safety in treating different diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayés, M., Rabasseda, X., Prous, JR.[2007]

The combination of enzalutamide and radium 223 (Ra 223) in treating metastatic castration-resistant prostate cancer (CRPC) was found to be safe and tolerable, with 87% of participants completing all treatment cycles without unexpected toxicities.

Patients reported improvements in quality of life and pain management, and there were no significant increases in serious adverse events, falls, or deaths, suggesting that this combination therapy could be beneficial for managing CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open Label Phase II Study of Enzalutamide With Concurrent Administration of Radium 223 Dichloride in Patients With Castration-Resistant Prostate Cancer. Shore, ND., Schellhammer, PF., Tutrone, RF., et al.[2021]

The combination of daratumumab, pomalidomide, and low-dose dexamethasone is shown to be a safe and effective treatment for relapsed/refractory multiple myeloma, with significant immune system enhancements observed in patients.

Treatment led to increased activation and proliferation of T cells, particularly CD8+ T cells, while also reducing certain immune cell types, suggesting a mechanism for improved immune-mediated tumor destruction without increasing exhausted T-cell phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. Pierceall, WE., Amatangelo, MD., Bahlis, NJ., et al.[2021]

In a study of 30 multiple myeloma patients who were refractory to daratumumab, treatment with pomalidomide-based combinations improved response rates from 37% to 53%.

Pomalidomide combinations were well tolerated, with no patients discontinuing treatment due to adverse events, and showed promising outcomes, including clinical stabilization in patients with extramedullary multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide combinations are a safe and effective option after daratumumab failure. Brioli, A., Gengenbach, L., Mancuso, K., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. [2019]

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

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. [2021]

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

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trial. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. [2021]

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

Gateways to clinical trials. [2007]

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

Open Label Phase II Study of Enzalutamide With Concurrent Administration of Radium 223 Dichloride in Patients With Castration-Resistant Prostate Cancer. [2021]

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

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Pomalidomide combinations are a safe and effective option after daratumumab failure. [2023]