Teclistamab/Talquetamab + Daratumumab for Multiple Myeloma

(REVIVE Trial)

Overseen By Michelle Armogan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Investigational agents, Live vaccines

Disqualifiers: HIV, Hepatitis B, COPD, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining Teclistamab or Talquetamab, both experimental treatments, with Daratumumab, a monoclonal antibody drug, can delay the onset of multiple myeloma, a type of blood cancer. It includes two groups: one receiving Teclistamab and Daratumumab, and the other receiving Talquetamab and Daratumumab. Individuals with smoldering multiple myeloma, who may be at high risk of progressing to a more serious disease, could be suitable for this trial. Participants should not have received prior systemic treatments for multiple myeloma. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have received prior systemic therapies for smoldering multiple myeloma, a 4-week period without treatment is required before starting the study treatment.

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

A previous study tested the combination of teclistamab and daratumumab for safety in patients with multiple myeloma. The results showed that this combination was generally well-tolerated. Some patients experienced side effects like anemia (low red blood cell count) and neutropenia (low white blood cell count), similar to those seen with other treatments.

Research indicates that the talquetamab and daratumumab combination has a similar safety profile. Patients also reported blood-related side effects, such as anemia and neutropenia. These side effects are common with this type of treatment and are generally manageable.

Both combinations have been studied in multiple myeloma patients with promising safety results. However, like any treatment, potential risks exist. Discussing any concerns with a healthcare professional before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they use innovative approaches to target this cancer. Unlike traditional treatments that primarily focus on killing cancer cells directly, Teclistamab and Talquetamab are designed to engage the body's immune system differently. Teclistamab targets the protein BCMA on myeloma cells, while Talquetamab targets GPRC5D, another protein found on these cancer cells, offering a more precise attack. When combined with Daratumumab, an antibody that also helps the immune system target myeloma, these treatments could potentially lead to better outcomes by tackling the cancer from multiple angles. This multi-targeted approach is what sets them apart and fuels optimism for more effective treatment options.

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

In this trial, participants will receive either the combination of Teclistamab and Daratumumab (Cohort A: Tec-Dara) or the combination of Talquetamab and Daratumumab (Cohort B: Tal-Dara). Research has shown that Teclistamab and Daratumumab together yield promising results for patients with multiple myeloma, a type of blood cancer. This combination helps patients live longer without disease progression. Even those who have undergone several prior treatments have demonstrated better survival outcomes with this combination.

Similarly, the combination of Talquetamab and Daratumumab has proven very effective. Recent data showed that all patients responded to this treatment, with 56% experiencing a complete response or better. These results suggest that this combination could provide strong and lasting benefits for those whose multiple myeloma has returned or not responded to previous treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

Carl Landgren, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults with high-risk smoldering multiple myeloma (SMM) who have not received prior treatments. Participants must be able to perform daily activities with minimal assistance, have good organ and marrow function, and agree to contraception if of childbearing potential. They cannot join if they have severe lung disease, certain heart conditions, active infections or other cancers, autoimmune diseases except some exceptions, or are on investigational drugs.

Inclusion Criteria

You have a certain amount of disease that can be measured using specific guidelines within the last 4 weeks.

My condition is confirmed as smoldering multiple myeloma.

My organs and bone marrow are working well.

Exclusion Criteria

Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment

I have not received a live vaccine in the last 4 weeks.

I am not allergic or unable to take any required medication for my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination treatment of Teclistamab and Daratumumab (Tec-Dara) or Talquetamab and Daratumumab (Tal-Dara) to delay the onset of multiple myeloma

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of MRD negativity and response rates

Up to 7 years

Extension

Long-term monitoring of clinical and biochemical progression-free survival, overall survival, and sustained MRD negativity

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Talquetamab
• Teclistamab

Trial Overview The REVIVE Study is testing whether combining Teclistamab with Daratumumab (Tel-Dara) or Talquetamab with Daratumumab (Tal-Dara) can delay the development of multiple myeloma in patients at high risk. The study will compare these two combination therapies to see which might be more effective.

How Is the Trial Designed?

Group I: Cohort B: Tal-Dara Experimental Treatment 2 Interventions

Dosing and treatment schedule for participants in this group will be determined after Cohort A is completed.

Group II: Cohort A: Tec-Dara Experimental Treatment 2 Interventions

Participants will receive the recommended dosage combination treatment Tec-Dara.

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?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Carl Ola Landgren, MD, PhD

Lead Sponsor

Trials

2

Recruited

80+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

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

Published Research Related to This Trial

Talquetamab, a bispecific T-cell engager targeting GPRC5D and CD3, has received accelerated approval in the USA and conditional marketing authorization in the EU for treating adults with relapsed or refractory multiple myeloma, highlighting its potential as a new treatment option.

This approval marks a significant milestone in the development of talquetamab, indicating its efficacy and safety in addressing a challenging form of cancer that has not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab: First Approval. Keam, SJ.[2023]

Daratumumab, now available in a subcutaneous form, significantly reduces administration time from 7 hours to just 3-5 minutes compared to the intravenous version, making it more convenient for patients.

The subcutaneous formulation also has lower rates of infusion-related reactions (less than 10% compared to 50% for intravenous), while maintaining similar efficacy and safety profiles, which enhances its overall usability in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. Sanchez, L., Richter, J., Cho, HJ., et al.[2021]

Teclistamab-cqyv is a bispecific T-cell engager antibody that effectively activates the immune system to target multiple myeloma cells, showing an overall response rate of over 60% in heavily pretreated patients.

The side effect profile of teclistamab-cqyv is more tolerable compared to other BCMA-targeted therapies, making it a suitable treatment option for elderly patients with relapsed or refractory multiple myeloma, and it has received FDA approval for use as monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. Hua, G., Scanlan, R., Straining, R., et al.[2023]

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 is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

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, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

Daratumumab, when combined with lenalidomide and dexamethasone or bortezomib and dexamethasone, significantly improves progression-free survival in patients with multiple myeloma who have received prior therapy, with reductions in the risk of disease progression or death by 63% and 61%, respectively.

The most common side effects reported were infusion reactions, diarrhea, and upper respiratory infections, with neutropenia and thrombocytopenia noted as important warnings, indicating that while daratumumab is effective, monitoring for these adverse reactions is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. Bhatnagar, V., Gormley, NJ., Luo, L., et al.[2022]

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 phase III CASTOR trial, the combination of daratumumab, bortezomib, and dexamethasone (D-Vd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma compared to bortezomib and dexamethasone (Vd) alone.

Patient-reported outcomes indicated that while there was no change in health-related quality of life during the first eight cycles of treatment, those continuing with daratumumab monotherapy reported improvements in global health status and pain thereafter, supporting the long-term benefits of D-Vd therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with bortezomib and dexamethasone: results from the phase III CASTOR trial. Hungria, V., Beksac, M., Weisel, KC., et al.[2021]

Citations

1. jnj.com jnj.com/innovativemedicine/emea/newsroom/oncology/talvey-talquetamab-and-darzalex-daratumumab-subcutaneous-sc-formulation-based-combination-shows-deep-and-durable-responses-in-patients-with-relapsed-or-refractory-multiple-myeloma

TALVEY®▼ (talquetamab) and DARZALEX® ... Updated data show 100 percent overall response rate, with 56 percent of patients achieving complete response or better with weekly dosing, supporting the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40983036/

Talquetamab plus daratumumab for the treatment of ... Talquetamab plus daratumumab demonstrated promising efficacy outcomes in heavily pretreated patients, with a safety profile consistent with ...

3. ashpublications.org ashpublications.org/blood/article/doi/10.1182/blood.2025029360/547408/Talquetamab-plus-daratumumab-for-the-treatment-of

Talquetamab plus daratumumab for the treatment of relapsed ... The combination demonstrated robust efficacy in patients with RRMM, including those with prior T-cell redirection therapy · The fully immune ...

4. ahdbonline.com ahdbonline.com/articles/ongoing-analyses-and-recent-data-for-talvey-in-multiple-myeloma

Ongoing Analyses and Recent Data for Talvey in Multiple ... MonumenTAL-1 (NCT03399799/NCT04634552) was a phase 1/2 study that had shown a 73% overall response rate (ORR) in 100 patients receiving a 0.4-mg ...

5. jnj.com jnj.com/media-center/press-releases/talvey-talquetamab-tgvs-and-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-combination-shows-deep-and-durable-responses-in-patients-with-relapsed-or-refractory-multiple-myeloma

TALVEY® (talquetamab-tgvs) and DARZALEX FASPRO ... Updated data show 100 percent overall response rate with 56 percent of patients achieving complete response or better with weekly dosing.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11798766/

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... Its safety profile is consistent with other BsAbs, with hematologic adverse events such as anemia and neutropenia commonly reported, alongside ...

7. jnjmedicalconnect.com jnjmedicalconnect.com/products/talvey/medical-content/darzalex-darzalex-faspro-adverse-event-hematologic-events-in-patients-with-relapsed-and-refractor

DARZALEX + DARZALEX FASPRO - Adverse Event A summary of safety data regarding the occurrence of hematologic events in patients with RRMM receiving DARZALEX® (daratumumab) and DARZALEX ...

8. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper199773.html

Paper: Talquetamab, a GPRC5D×CD3 Bispecific Antibody ... Conclusions: This novel, fully immune combination regimen of tal-DR showed high ORR and rapid responses in pts with NDMM with 3.5-10.5 months of ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06577025

NCT06577025 | A Study of Different Sequences of Cilta-cel ... The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start ...