What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as bispecific antibodies like Talquetamab and Teclistamab, and combination therapies involving pomalidomide, bortezomib, and dexamethasone, are associated with several side effects. These include high rates of grade 3 or 4 neutropenia, infections, and pneumonia. Other frequent side effects are gastrointestinal issues (diarrhea, constipation), fatigue, upper respiratory tract infections, and infusion-related reactions. Specific to daratumumab, there is an increased risk of neutropenia, lymphocytopenia, and viral reactivations such as herpes zoster. Patients on these therapies often experience a range of hematologic and non-hematologic toxicities, necessitating careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Myeloma, including bispecific antibodies and other novel agents. Bispecific T cell engagers (BiTEs) like teclistamab, which targets BCMA and CD3, have shown high rates of deep and durable responses. Other notable FDA-approved treatments include chimeric antigen receptor T cells (CAR-T) such as idecabtagene vicleucel and ciltacabtagene autoleucel, which also target BCMA. Additionally, the anti-BCMA antibody-drug conjugate belantamab mafodotin has been approved. These treatments are similar to Talquetamab, which targets GPRC5D and CD3, and are part of the evolving landscape of immunotherapy in Multiple Myeloma.

What other types of research exist?

Promising novel alternatives to Talquetamab for Multiple Myeloma patients include: 1) Bispecific antibodies like Teclistamab (targeting BCMA and CD3), 2) CAR T-cell therapies such as Idecabtagene Vicleucel (targeting BCMA), 3) Antibody-drug conjugates like Belantamab Mafodotin (targeting BCMA), and 4) Combination therapies involving Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Elotuzumab, Pomalidomide, and Dexamethasone (EPd). These alternatives have shown promising results in clinical trials and offer different mechanisms of action for treating Multiple Myeloma.

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CAR T-cell Therapy

Talquetamab Combinations for Multiple Myeloma (MonumenTAL-6 Trial)

Q: What is the mechanism of action of this treatment?

Multiple Myeloma treatments often target specific pathways to inhibit cancer cell growth and survival. Talquetamab, a bispecific antibody, targets GPRC5D on myeloma cells and CD3 on T cells, redirecting T cells to kill myeloma cells. Proteasome inhibitors like bortezomib disrupt protein degradation, leading to cancer cell apoptosis. Immunomodulatory drugs such as pomalidomide enhance immune response and inhibit myeloma cell proliferation. Monoclonal antibodies like daratumumab target CD38 on myeloma cells, promoting immune-mediated destruction. These mechanisms are crucial as they offer targeted approaches to manage and potentially overcome the disease, improving patient outcomes.

Phase 3

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented multiple myeloma as defined by the criteria below: (a) multiple myeloma diagnosis according to the international myeloma working group (IMWG) diagnostic criteria (b) measurable disease at screening as assessed by central laboratory, defined by any of the following: (i) serum M-protein level greater than or equal to (>=) 0.5 gram per deciliter (g/dL); or (ii) urine M-protein level >= 200 milligram (mg) per 24 hours; or (iii) light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio

Relapsed or refractory disease as defined below: a) Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years 5 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing two new drug combinations to treat multiple myeloma. The combinations include talquetamab with either pomalidomide or teclistamab. These drugs help the immune system better identify and destroy cancer cells. The goal is to see if these new combinations work better than existing treatments.

Who is the study for?

This trial is for people with multiple myeloma that has come back or hasn't responded to treatment, including an anti-CD38 antibody and lenalidomide. Participants should be fairly active (ECOG score of 0-2), not pregnant or planning pregnancy soon, and have measurable disease levels according to specific medical criteria.

What is being tested?

The study compares the effectiveness of talquetamab with pomalidomide (Tal-P) or talquetamab with teclistamab (Tal-Tec) against two other drug combinations: elotuzumab with pomalidomide and dexamethasone (EPd), or pomalidomide with bortezomib and dexamethasone (PVd).

What are the potential side effects?

Possible side effects include immune system reactions, infections, fatigue, nausea, nerve damage from Bortezomib, blood clots from Pomalidomide, high blood sugar from Dexamethasone, and infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with multiple myeloma and meet the specific blood or urine test criteria.

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My cancer came back or didn't respond well to treatment.

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I can care for myself and am up and about more than 50% of my waking hours.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years 5 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years 5 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 years 5 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression Free Survival (PFS)

Secondary study objectives

Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30

Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EQ-5D-5L

Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey

+17 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm B: Talquetamab + Teclistamab (Tal-Tec)Experimental Treatment3 Interventions

Participants will receive teclistamab in combination with talquetamab both as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

Group II: Arm A: Talquetamab + Pomalidomide (Tal-P)Experimental Treatment3 Interventions

Participants will receive talquetamab as subcutaneous (SC) injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

Group III: Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd)Active Control4 Interventions

Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidamide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dexamethasone

2007

Completed Phase 4

~2650

Pomalidomide

2011

Completed Phase 2

~1020

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Myeloma treatments often target specific pathways to inhibit cancer cell growth and survival. Talquetamab, a bispecific antibody, targets GPRC5D on myeloma cells and CD3 on T cells, redirecting T cells to kill myeloma cells. Proteasome inhibitors like bortezomib disrupt protein degradation, leading to cancer cell apoptosis. Immunomodulatory drugs such as pomalidomide enhance immune response and inhibit myeloma cell proliferation. Monoclonal antibodies like daratumumab target CD38 on myeloma cells, promoting immune-mediated destruction. These mechanisms are crucial as they offer targeted approaches to manage and potentially overcome the disease, improving patient outcomes.