Talquetamab + Daratumumab/Pomalidomide for Multiple Myeloma

(MonumenTAL-3 Trial)

Not currently recruiting at 364 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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of a new combination of treatments for multiple myeloma, a type of blood cancer. Researchers are testing various combinations of four drugs: talquetamab (also known as Talvey), daratumumab, pomalidomide, and dexamethasone, to identify the most effective one. Individuals with multiple myeloma that has recurred or not responded well to previous treatments might be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of talquetamab and daratumumab is generally safe, though it can cause common side effects such as low blood cell levels, including anemia (low red blood cells) and neutropenia (low white blood cells). The safety profile of this combination is similar to each drug used individually.

For the combination of daratumumab, pomalidomide, and dexamethasone, about 50% of patients reported serious side effects. However, no new safety issues have emerged, except for an increase in low white blood cell counts (neutropenia).

Talquetamab has recently been approved for certain patients, indicating that its safety has been well studied. However, like any treatment, risks and side effects may occur.

These findings provide insight into the safety of these treatments. It is important for anyone considering joining a trial to discuss these aspects with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving talquetamab for multiple myeloma because they offer a fresh approach compared to traditional therapies. Unlike standard treatments, which typically rely on drugs like lenalidomide or bortezomib, talquetamab is a novel bispecific antibody that targets both the cancerous cells and T-cells, effectively bridging them to promote a more robust immune response. Additionally, the subcutaneous (SC) delivery of talquetamab and daratumumab in these combinations is more convenient and potentially less invasive than conventional intravenous methods. This innovative mechanism and delivery method could mean more effective and patient-friendly treatment options for individuals battling multiple myeloma.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research shows that using talquetamab with daratumumab, which participants may receive in Arm C, has promising results for treating relapsed or refractory multiple myeloma. Studies found that all patients responded to this treatment, with more than half experiencing a complete recovery or better. In Arm A, talquetamab is combined with daratumumab and pomalidomide, and about 82% of patients responded well, indicating strong potential for effectiveness. Additionally, participants in Arm B will receive daratumumab, pomalidomide, and dexamethasone, which resulted in a 94% response rate, with 67% of patients achieving a complete recovery or better. These findings suggest that all treatment combinations in this trial could be very effective for multiple myeloma. ^{4 5 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7876/527017/Efficacy-and-Safety-of-Daratumumab-Plus

Efficacy and Safety of Daratumumab Plus Pomalidomide and ... The overall response rate (ORR) was 94% with 67% achieving a complete response or better. After a median follow-up of 12.5 months (range 1-17), ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39237427/

Final Overall Survival From MM-014 Pomalidomide plus daratumumab and dexamethasone (DPd) showed promising efficacy (median follow-up 28.4 months), as previously reported.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025028861

Efficacy and Safety of Daratumumab, Pomalidomide ... Daratumumab-based triplet regimens have demonstrated efficacy in relapsed or refractory multiple myeloma (RRMM).

4. esmoopen.com esmoopen.com/article/S2059-7029(24)01854-4/fulltext

Outcomes and prognostic indicators in daratumumab ... This study supports EloPd as an effective treatment option in Dara-R MM patients, providing valuable disease control and acting as a potential ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37793772/

Subcutaneous daratumumab plus pomalidomide and ... Daratumumab plus pomalidomide and dexamethasone significantly improved progression-free survival versus pomalidomide and dexamethasone.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571914/

Efficacy and Safety of Daratumumab, Pomalidomide, and ... Daratumumab-based combinations with pomalidomide/dexamethasone (DPd), or bortezomib/dexamethasone (DVd), have shown activity in relapsed/ ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00128-5/abstract

Daratumumab plus pomalidomide and dexamethasone ... Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5570682/

Daratumumab plus pomalidomide and dexamethasone in ... No new safety signals were observed with daratumumab plus pomalidomide and dexamethasone, except for increased neutropenia. Daratumumab plus pomalidomide and ...