Daratumumab + T Cell Redirecting Antibodies for Multiple Myeloma

Recruiting at 37 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

290 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) for each treatment combination (between daratumumab plus talquetamab and teclistamab plus daratumumab with or without pomalidomide) and to characterize the safety of each RP2D for selected treatment combinations.

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 have been treated with an anti-CD38 therapy like daratumumab in the past 3 months, you may not be eligible to participate.

What data supports the effectiveness of the drug Daratumumab for treating multiple myeloma?

Research shows that Daratumumab, when used alone or with other drugs, can effectively treat multiple myeloma by targeting and killing cancer cells. It has been shown to provide significant benefits, including rapid and lasting responses, in patients who have not responded to other treatments. ^{1 2 3 4 5}

Is the combination of Daratumumab and T Cell Redirecting Antibodies safe for humans?

Daratumumab, used alone or in combination with other drugs for multiple myeloma, is generally well tolerated. Common side effects include infusion-related reactions (mild to moderate) and blood-related issues like low platelet or white blood cell counts. ^{1 3 5 6 7}

How is the drug combination of Daratumumab, Talquetamab, and Teclistamab unique for treating multiple myeloma?

This drug combination is unique because it combines Daratumumab, a monoclonal antibody targeting CD38 on myeloma cells, with T cell redirecting antibodies like Talquetamab and Teclistamab, which help the immune system target and destroy cancer cells more effectively. This approach leverages different mechanisms to enhance the immune response against multiple myeloma, potentially offering a more comprehensive treatment strategy. ^{2 3 7 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with multiple myeloma who've had at least three prior treatments, including specific drugs like proteasome inhibitors and immunomodulatory drugs. They should be relatively healthy (ECOG grade of 0 or 1) and not pregnant if female. People can't join if they've recently used certain anti-CD38 therapies, received live vaccines, or have active hepatitis or central nervous system involvement by the cancer.

Inclusion Criteria

My condition did not improve after treatments including a PI and an IMiD.

You must have a specific amount of disease that can be measured according to certain rules.

My multiple myeloma diagnosis follows international guidelines.

Exclusion Criteria

I haven't had CD38 therapy in the last 3 months or stopped it due to side effects.

I haven't had a live vaccine in the last 4 weeks or it was approved by the study sponsor.

You have a positive test for hepatitis B or an active hepatitis C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part 1: Dose Escalation

Participants will be assigned to different combinations of daratumumab, teclistamab, talquetamab, and pomalidomide to determine the recommended Phase 2 doses (RP2Ds).

Up to 52 weeks

Treatment - Part 2: Dose Expansion

Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.

Up to 48 weeks

Post-treatment Follow-up

Participants are monitored for safety and effectiveness after treatment.

16 weeks

Long-term Extension

Participants may continue to receive study treatment if they are benefiting, until the study drug receives marketing authorization or a long-term extension rollover study commences.

Long-term

Treatment Details

Interventions

• Daratumumab
• Pomalidomide
• Talquetamab
• Teclistamab

Trial Overview The study is testing combinations of Daratumumab with Talquetamab or Teclistamab, with some groups also getting Pomalidomide. The goal is to find safe doses for these combos and see how well they work together in treating multiple myeloma.

Participant Groups

Group I: Part 2: Dose Expansion Experimental Treatment 4 Interventions

Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.

Group II: Part 1: Dose Escalation Experimental Treatment 4 Interventions

Participants will be assigned to either a combination of 1) daratumumab plus teclistamab or 2) daratumumab plus talquetamab or 3) daratumumab plus talquetamab plus pomalidomide or 4) daratumumab plus teclistamab plus pomalidomide.

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

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 shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

A 70-year-old patient with advanced multiple myeloma, who had previously undergone five lines of therapy, achieved a stringent complete response and over 3.5 years of remission with daratumumab monotherapy, significantly exceeding the median response duration of 7.6 months for similar patients.

The patient's treatment with daratumumab led to notable changes in his immune profile, including expansion of CD8+ T-cells and a decrease in regulatory T-cells, indicating a strong adaptive immune response that supports the drug's immunomodulatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. Usmani, SZ., Khan, I., Chiu, C., et al.[2022]

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 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]

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]

References

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

Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

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

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. [2022]

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

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

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

Daratumumab: First Global Approval. [2018]

8. France pubmed.ncbi.nlm.nih.gov

[Daratumumab for multiple myeloma]. [2018]

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

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