Talquetamab for Multiple Myeloma

Overseen By Lupita Chen

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Larysa Sanchez

Must not be taking: T-cell-engaging antibodies

Disqualifiers: Active CNS involvement, Plasma cell leukemia, Active malignancies, Uncontrolled diabetes, 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

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called talquetamab for individuals with multiple myeloma, a type of blood cancer, whose cancer has returned or not responded to at least two previous treatments. Talquetamab aids the immune system in targeting and fighting cancer cells. If the initial treatment proves ineffective, the addition of daratumumab, an antibody therapy, may enhance the treatment. Suitable candidates have relapsed or hard-to-treat multiple myeloma and have tried at least two other therapies without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing early access to potentially effective therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain prior treatments, like monoclonal antibody treatment for multiple myeloma, must be stopped at least 21 days before the study. 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 has shown that talquetamab, a treatment for multiple myeloma, has been promising in earlier studies. In one study with patients who had already tried many treatments, 70% responded well to talquetamab. Importantly, most patients tolerated it well. For instance, only a few experienced serious skin rashes, which could be treated with steroids.

When combined with another drug, daratumumab, the side effects remained similar to when each drug was used alone. This indicates that the side effects did not significantly worsen when both drugs were used together. Common side effects included low blood cell counts, such as anemia (low red blood cells) and neutropenia (low white blood cells), which are common with many cancer treatments.

Overall, while there are risks, the safety data suggest that talquetamab, both alone and with daratumumab, is manageable for patients. This is especially important for those who have not had success with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Talquetamab is unique because it targets GPRC5D, a protein highly expressed on multiple myeloma cells, offering a new mechanism of action compared to standard treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies targeting CD38. This novel approach may provide options for patients who have become resistant to current therapies. Additionally, talquetamab is administered subcutaneously, which can be more convenient and potentially less burdensome than intravenous treatments. Researchers are excited about its potential to effectively manage multiple myeloma with a different biological target, possibly leading to improved outcomes for patients.

What evidence suggests that talquetamab might be an effective treatment for multiple myeloma?

Research shows that talquetamab holds promise for treating relapsed or refractory multiple myeloma, a type of blood cancer. In this trial, one group of participants will receive talquetamab as a monotherapy. Studies have shown that 70 out of every 100 patients, who had already tried many other treatments, experienced cancer improvement with talquetamab. Another group will test talquetamab combined with daratumumab. Previous research indicates even better results, with 82 out of every 100 people responding positively. These findings are encouraging, especially for those with limited options after other treatments have failed. ^{2 6 7 8 9}

Who Is on the Research Team?

Larysa Sanchez, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for elderly patients with multiple myeloma who have experienced an early relapse after 1-3 prior therapies. They should not be candidates for aggressive treatments like stem cell transplantation and must have been refractory to at least three major drug classes.

Inclusion Criteria

Clinical laboratory values meeting specific criteria during the Screening Phase

Human immunodeficiency virus-positive participants meeting specific criteria

Agreement to wear a condom and not donate sperm for reproduction

Exclusion Criteria

Specific medical conditions or diseases likely to interfere with study procedures

Disabling psychiatric conditions or altered mental status

History of non-compliance with medical treatments

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive talquetamab SC monotherapy starting with three step-up doses followed by the standard 800 μg/kg dose every other week. Cycles are 28 days long.

12 weeks

Monthly response assessment

Treatment Part 2

For participants who proceed to part 2, talquetamab is continued and daratumumab is added. Daratumumab is administered weekly for 2 cycles, every other week for 4 cycles, then monthly.

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Talquetamab

Trial Overview The study tests subcutaneous Talquetamab, a new antibody that targets myeloma cells, in these patients. If there's no improvement after three cycles, Daratumumab will be added. The goal is to find an effective yet tolerable treatment for this group.

How Is the Trial Designed?

Group I: Talquetamab SC monotherapy Experimental Treatment 1 Intervention

In part 1, patients will receive talquetamab SC monotherapy starting with three step-up doses followed by the standard 800 μg/kg dose every other week. Cycles will be 28 days long. Response will be assessed monthly according to IMWG criteria, and patients who have PD after completing at least 1 cycle of talquetamab or who fail to attain ≥ PR after completion of cycle 3 will proceed to part 2 only if not previously refractory to an anti-CD38 monoclonal antibody. Patients refractory to an anti-CD38 mAb will not be allowed in Part 2. patients who are refractory to an anti-CD38 mAb and PD at any point will be taken off study and not proceed to Part 2. patients who are refractory to an anti-CD38 mAb and achieve a response \<PR after 3 cycles (stable disease or minimal response) will continue on talquetamab monotherapy until PD or be taken off study per investigator discretion if it is deemed that subject will not continue to derive clinical benefit from talquetamab monotherapy.

Group II: Talqeutemab SC + Daratumumab SC Experimental Treatment 2 Interventions

For participants who proceed to part 2, talquetamab will be continued at 800 μg/kg every other week but daratumumab will be initiated at the standard dose (weekly for 2 cycles, every other week for 4 cycles, monthly thereafter). In part 2, participants will continue talquetamab and daratumumab until PD, unacceptable toxicity or other reasons for discontinuing treatment, withdrawal from study. Patients in part 1 and part 2 who achieve VGPR or better after receiving at least 4 cycles of talquetamab in the respective part can be transitioned to every 4 week dosing.

Who Is Running the Clinical Trial?

Larysa Sanchez

Lead Sponsor

Trials

2

Recruited

40+

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

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]

In the phase 1 MonumenTAL-1 study involving patients with refractory or relapsed multiple myeloma, two doses of talquetamab (405 μg/kg weekly and 800 μg/kg every other week) were found to be well tolerated, with most side effects being mild or moderate, including cytokine release syndrome (CRS).

The treatment showed promising efficacy, with most participants experiencing a reduction in cancer signs and a median duration of response of 8-10 months, indicating talquetamab's potential as a new option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of the MonumenTAL-1 study of talquetamab in people with relapsed or refractory multiple myeloma. Chari, A., Askari, E., Caers, J., et al.[2023]

Belantamab mafodotin (BLENREP) received accelerated FDA approval for treating relapsed or refractory multiple myeloma in adults who have undergone at least four prior therapies, showing an overall response rate of 31% to 34% in the DREAMM-2 trial with 2.5 or 3.4 mg/kg doses.

The most common side effect was keratopathy, affecting 71% to 77% of patients, leading to a boxed warning for ocular toxicity, indicating the need for careful monitoring and a restricted distribution program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. Baines, AC., Ershler, R., Kanapuru, B., et al.[2023]

In the MonumenTAL-1 trial, nearly 75% of the 288 patients with relapsed/refractory multiple myeloma showed significant anticancer effects from the investigational drug talquetamab.

Talquetamab is a first-in-class bispecific antibody that targets GPRC5D on malignant plasma cells while sparing normal cells, effectively activating T cells to mount an immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MonumenTAL Results for Talquetamab in Myeloma. [2023]

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]

Talquetamab, a bispecific antibody targeting GPRC5D and CD3, shows similar efficacy and durability of response in treating relapsed or refractory multiple myeloma compared to teclistamab, the first bispecific antibody approved for this condition.

While talquetamab has a lower incidence of infections than teclistamab, it presents unique side effects related to skin, oral, and nails, yet remains a well-tolerated and effective treatment option for patients with heavily pretreated multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. Liu, L., Krishnan, A.[2023]

Three new bispecific antibodies—teclistamab, elranatamab, and talquetamab—have received accelerated FDA approval for treating relapsed/refractory multiple myeloma, indicating their potential efficacy in this challenging condition.

While these agents show promise, the medical community is currently awaiting results from randomized phase III clinical trials to better understand their effectiveness compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. Firestone, R., Lesokhin, AM., Usmani, SZ.[2023]

Belantamab mafodotin is a newly approved treatment for relapsed or refractory multiple myeloma, showing an overall response rate of 31% and a median progression-free survival of 2.9 months in patients who have undergone at least four prior therapies.

While the treatment is generally well tolerated, it is associated with notable ocular toxicities, which require careful management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Ocular Toxicity in Patients Receiving Belantamab Mafodotin. Lu, R., Morphey, A., Diaz, F., et al.[2023]

Citations

1. 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.

2. targetedonc.com targetedonc.com/view/talquetamab-combo-yields-high-responses-in-heavily-pretreated-myeloma

Talquetamab Combo Yields High Responses in Heavily ... Talquetamab and daratumumab combination achieved an 82.4% overall response rate in relapsed/refractory multiple myeloma patients, with a median ...

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... The TRiMM‐2 study (NCT04108195) is a trial that evaluated the use of talquetamab in combination with daratumumab, with or without pomalidomide, ...

4. 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 ...

5. 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, ...

6. 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

7. talveyhcp.com talveyhcp.com/safety/

Side Effects & Safety Profile | TALVEY® (talquetamab-tgvs) HCP TALVEY can cause serious, life-threatening neurologic toxicity or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome ( ...

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7860/527083/Real-World-Safety-and-Efficacy-of-Talquetamab-for

Real-World Safety and Efficacy of Talquetamab for Patients ... One potential treatment-related death was reported; 21% of the patients had died at the time of data cut-off (7/1/24) with 83% of deaths ...

9. cancernetwork.com cancernetwork.com/view/talquetamab-elicits-durable-responses-survival-in-r-r-multiple-myeloma

Talquetamab Elicits Durable Responses, Survival in R/R ... The safety profile of talquetamab continued to show a lower high-grade infection risk relative to other approved anti-BCMA bispecific ...