Multi-Target Immunotherapy for Multiple Myeloma

Overseen By Joseph A Holley

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arkansas

Must not be taking: Corticosteroids, Monoclonal antibodies

Disqualifiers: Hypertension, Diabetes, Asthma, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether using two immunotherapy drugs, teclistamab and talquetamab, at different times can extend the lives of people with high-risk Multiple Myeloma. The trial includes several stages of chemotherapy, and based on a participant's test results, they might also receive a stem cell transplant. It seeks participants with newly diagnosed Multiple Myeloma who need treatment and show signs of high-risk disease, such as certain genetic changes or specific symptoms. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it allows the use of bisphosphonates and localized radiation, suggesting some medications might be allowed. It's best to discuss your specific medications with the trial team.

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

Research shows that both teclistamab and talquetamab have been tested in patients with multiple myeloma, providing information about their safety. The FDA and EMA have recently approved talquetamab for patients who have tried several other treatments, indicating a known safety profile. Although side effects with talquetamab are common, they are usually manageable.

Teclistamab has also been studied and found to have an acceptable safety profile for patients with relapsed or hard-to-treat multiple myeloma. While side effects can occur, they are often tolerable.

Potential trial participants should know that these treatments have undergone extensive testing, providing reliable information about their safety, even though side effects may still happen. Always consult a healthcare provider to understand what these findings mean for individual circumstances. ^{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 focus on harnessing the power of the immune system in new ways. Talquetamab and teclistamab are both types of bispecific antibodies, which are designed to target cancer cells more precisely by connecting them directly to immune cells that can destroy them. This targeted approach is different from traditional treatments like chemotherapy, which can affect both cancerous and healthy cells. Additionally, by combining these novel antibodies with existing treatments like daratumumab and lenalidomide, there's potential for more effective and longer-lasting responses in patients, especially those with minimal residual disease.

What evidence suggests that this trial's treatments could be effective for Multiple Myeloma?

This trial will evaluate the effectiveness of teclistamab and talquetamab in treating multiple myeloma, a type of blood cancer. Studies have shown that using teclistamab and talquetamab together is effective, with 80% of patients responding well and 52% having no detectable cancer after treatment. Additional studies indicate that these drugs can help patients who have not succeeded with other treatments. This combination has shown promise for patients whose multiple myeloma has returned or is difficult to treat. These findings suggest that teclistamab and talquetamab may help people with high-risk multiple myeloma live longer. Participants in this trial will receive these treatments as part of different study arms based on their MRD status. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals with high-risk Multiple Myeloma. Participants must be suitable for intensive chemotherapy and stem cell collection. Those who are MRD positive will undergo a stem cell transplant, while MRD negative participants will not.

Inclusion Criteria

I have not had more than two months of treatment for my MM, but I may have had bisphosphonates or localized radiation.

Patients must have signed an IRB-approved informed consent form.

Female subjects must not donate eggs during the study and for 6 months after the last dose of study medications.

Exclusion Criteria

Pregnant, breastfeeding, planning pregnancy, or planning to father a child during the study period.

I have a serious heart condition.

Patients seropositive for HIV, hepatitis B, or hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction treatment with daratumumab (Dara)-KRD for 4 cycles to obtain immediate disease control, reduce tumor bulk and minimize the risk of subsequent cytokine release syndrome (CRS). Peripheral blood stem cell (PBSC) will be harvested after induction treatment.

16 weeks

Immunotherapy 1

Participants receive teclistamab+daratumumab followed sequentially by talquetamab+daratumumab each for 4 cycles.

16 weeks

MRD-based Consolidation

For MRD-negative participants, teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles. For MRD-positive participants, a single melphalan (MEL)-based hematopoietic stem cell transplantation (HSCT) followed by the same immunotherapy regimen.

16 weeks

Maintenance Therapy

2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melphalan
• talquetamab
• teclistamab

Trial Overview The study tests if using teclistamab and talquetamab at different stages improves survival in MM patients. It includes induction chemo, two phases of immunotherapy, possible stem cell transplant, followed by maintenance therapy with daratumumab and lenalidomide.

How Is the Trial Designed?

Group I: MRD-positive Experimental Treatment 1 Intervention

Subjects who are MRD-positive (a threshold of 10\^5) will receive a single melphalan (MEL)-based hematopietic stem cell transplantation (HSCT) followed by teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles followed by a 2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression. MRD status with classification threshold of 10\^5 will be assessed by standardized flow cytometry.

Group II: MRD-negative Experimental Treatment 1 Intervention

Subjects who are MRD-negative (a threshold of 10\^5) will be given teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles followed by 2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression.

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Janssen Research & Development, LLC

Industry 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

Citations

1. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/real-world-data-shows-teclistamab-can-benefit-many-multiple-myeloma-patients-who-would-have-been-ineligible-for-pivotal-trial/

Real-world Data Shows Teclistamab Can Benefit Many ... Forty percent exhibited “very good partial responses,” including 43% of the 58 patients whose disease had been previously treated with the ...

2. ashpublications.org ashpublications.org/ashclinicalnews/news/8519/Talquetamab-Plus-Teclistamab-Effective-for

Talquetamab Plus Teclistamab Effective for Relapsed or ... Eighty percent of patients receiving the recommended phase II dose responded: 52% experienced a complete response (CR), and 48% had a CR or ...

3. nature.com nature.com/articles/s41408-025-01314-9

Outcomes of teclistamab in patients with relapsed/ ... The median overall PFS for all patients with BCMA-DT was 4.8 months, closely aligning with our findings, and the 9-month OS rate was 60% [27].

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40352937/

Effectiveness and safety of teclistamab for relapsed or ... Teclistamab continues to be a promising and effective treatment option for RRMM patients, including those previously exposed to BCMA-targeted therapies.

5. onclive.com onclive.com/view/talquetamab-teclistamab-may-address-need-for-improved-survival-outcomes-in-r-r-myeloma-with-extramedullary-disease

Talquetamab/Teclistamab May Address Need for Improved ... Shahzad Raza, MD, discusses updated outcomes with talquetamab and teclistamab in relapsed/refractory multiple myeloma with extramedullary

6. nature.com nature.com/articles/s41408-025-01386-7

Talquetamab in relapsed refractory multiple myeloma Our analysis of AEs highlights some important safety considerations for the clinical use of talquetamab, as AEs were frequent but manageable.

7. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00385-5/fulltext

Safety and activity of talquetamab in patients with relapsed ... Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1–2 study

8. ashpublications.org ashpublications.org/blood/article/144/23/2375/517467/Efficacy-and-safety-of-teclistamab-in-patients

Efficacy and safety of teclistamab in patients with relapsed ... Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs).

10. onclive.com onclive.com/view/teclistamab-based-induction-regimens-deepen-responses-in-newly-diagnosed-multiple-myeloma

Teclistamab-Based Induction Regimens Deepen ... Raab, MD, discusses updated MRD negativity and safety data with teclistamab plus SOC induction regimens in newly diagnosed multiple myeloma.