Daratumumab + T Cell Redirecting Antibodies for Multiple Myeloma

Not currently recruiting at 38 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Anti-CD38 therapy

Disqualifiers: Active CNS involvement, Hepatitis B, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for people with multiple myeloma, a type of blood cancer. The researchers aim to find the best dose and assess the safety of using different drug combinations, including daratumumab (Darzalex), talquetamab, and teclistamab, sometimes with pomalidomide. Participants may qualify if they have been diagnosed with multiple myeloma and have tried at least three other treatments, including specific drug types, without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive potentially groundbreaking therapies.

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.

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

Research has shown that the combination of daratumumab and teclistamab is generally well-tolerated. One study found that this combination significantly improved outcomes for patients with multiple myeloma. Common side effects, such as upper respiratory infections and low white blood cell counts, can be managed.

When combined with talquetamab, daratumumab has demonstrated promising safety. Updated data showed a 100% overall response rate, with some patients experiencing complete responses, indicating the treatment was effective and safe for patients with relapsed or hard-to-treat multiple myeloma.

For the combination of daratumumab, teclistamab, and pomalidomide, research has also shown positive results. Patients experienced longer periods without disease progression during and after treatment.

Finally, the combination of daratumumab, talquetamab, and pomalidomide has shown strong and lasting benefits, with patients experiencing long-term improvements. While these treatments are still under study, results so far suggest they are generally safe, with some common and manageable side effects. ^{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 combine daratumumab with innovative T cell-redirecting antibodies like talquetamab and teclistamab. Unlike traditional therapies that mostly target the cancer cells directly, these treatments work by engaging the immune system more actively. Talquetamab and teclistamab act as bridges, directing T cells to attack the myeloma cells more effectively. This approach offers a novel way to potentially enhance the immune response against the cancer, which could lead to better outcomes for patients.

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

This trial will evaluate different combinations of treatments for multiple myeloma. Participants may receive a combination of daratumumab and teclistamab, which research has shown to be very effective, with all patients in studies responding to this treatment. This combination also helps patients live longer without disease progression and improves overall survival compared to standard treatments.

Another group in this trial will receive daratumumab and talquetamab, which has shown promising results, with all patients responding and more than half having no detectable cancer after treatment.

Additionally, some participants will receive combinations that include pomalidomide, which further enhances treatment effectiveness. These findings suggest that these treatment combinations can effectively manage multiple myeloma. ^{6 7 8 9 10}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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, 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]

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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428465/

S192: TALQUETAMAB (TAL) + DARATUMUMAB ... Median time to first response was 1 mo (range 0.9–8.3); at 12 mo, 86% of responders (89% of pts with ≥CR) still had responses. At data cutoff, 84% of responders ...

3. prnewswire.com prnewswire.com/news-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-302260992.html

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, ...

4. 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 ...

5. jnj.com jnj.com/media-center/press-releases/tecvayli-plus-darzalex-faspro-combination-regimen-significantly-improves-progression-free-survival-and-overall-survival-versus-standard-of-care

TECVAYLI® plus DARZALEX FASPRO® combination ... In transplant-eligible patients with newly diagnosed multiple myeloma, a 100 percent overall response rate was achieved when given as the first ...

6. 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.

7. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/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. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761036s044lbl.pdf

Darzalex - accessdata.fda.gov In this pooled safety population, the most common adverse reactions (≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, ...

9. darzalex.com darzalex.com/

Official Consumer Website | DARZALEX® & DARZALEX ... DARZALEX FASPRO® is a prescription medicine used to treat adult patients with multiple myeloma: ... It is not known if DARZALEX FASPRO® is safe and effective in ...

10. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/170456-316022/daratumumab-intravenous

Daratumumab: uses, dosing, warnings, adverse events, ... Daratumumab/hyaluronidase-fihj is also used for the treatment of multiple myeloma in adults in combination with bortezomib, lenalidomide, and dexamethasone for ...