Talquetamab + Ciltacabtagene Autoleucel for Multiple Myeloma

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical College of Wisconsin

Must not be taking: Antiretrovirals, Cytotoxic chemotherapy

Disqualifiers: CNS involvement, Plasma cell leukemia, Severe cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating multiple myeloma, a type of blood cancer that often recurs after treatment. The researchers are testing the safety of using a drug called talquetamab before administering a CAR T-cell therapy known as cilta-cel (ciltacabtagene autoleucel). This trial targets individuals who have tried other treatments for multiple myeloma but continue to experience the disease. Those with multiple myeloma that has not responded well to past treatments and affects daily life might find this trial suitable. 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 this new therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop certain treatments before joining. Specifically, you must not have had certain therapies like high-dose chemotherapy, specific antibodies, or radiation therapy within a specified time before enrollment. However, the protocol does not specify all medications, so it's best to discuss your current medications with the trial team.

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

A previous study found talquetamab to be well-tolerated by patients with relapsed or refractory multiple myeloma. The most common side effects, such as skin rash and changes in taste, were manageable. Research has shown that ciltacabtagene autoleucel, also known as cilta-cel, received approval in 2022 for similar conditions, indicating a strong safety profile. These treatments have been studied for their safety and have shown promising results. Although this trial is in an early phase, the data so far supports their use in people with this type of cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Talquetamab and Ciltacabtagene autoleucel for multiple myeloma because they represent a novel approach to treatment. Unlike traditional therapies such as chemotherapy, these treatments involve leveraging the body's own immune system. Talquetamab works as a bridging therapy and targets a specific protein on myeloma cells, which is different from the broader attack seen with standard chemotherapy. Ciltacabtagene autoleucel is a CAR T-cell therapy, which means it involves modifying a patient's T-cells to better recognize and destroy cancer cells. This combination offers a targeted and potentially more effective way to treat relapsed or refractory multiple myeloma.

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

Research has shown that talquetamab is effective for patients with multiple myeloma who have tried several other treatments. Talquetamab targets specific proteins on cancer cells, aiding the immune system in fighting the disease. In this trial, participants will receive talquetamab as a bridging therapy during CAR T-cell manufacturing, followed by Ciltacabtagene autoleucel (a type of CAR T-cell therapy). Studies indicate that using talquetamab before Ciltacabtagene autoleucel may help control the cancer in the short term. Talquetamab has been approved for use when the cancer returns or does not respond to other treatments, highlighting its effectiveness for these patients. This combination approach aims to enhance the immune system's ability to attack and control the cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with relapsed and refractory multiple myeloma, meaning their cancer has returned or didn't respond to treatment. Specific eligibility details are not provided, but typically participants must meet certain health standards and have a history of the condition being studied.

Inclusion Criteria

Have measurable disease: Serum M-protein level ≥ 1.0 g/dL, or Urine M-protein level ≥ 200 mg/24 hours, or In patients without a measurable M-protein, an involved light chain level ≥ 10 mg/dL and an abnormal free light chain ratio

I meet the FDA guidelines for using talquetamab.

Ability to understand a written informed consent document, and the willingness to sign it

Exclusion Criteria

Prior treatment: Adoptive T-cell therapy (e.g., CAR T-cell therapy) at any time prior to enrollment, Bispecific antibody, investigational or approved, irrespective of its target, at any time prior to enrollment, Use of talquetamab prior to enrollment, Any therapy targeting BCMA or GPRC5D, including but not limited to antibody-drug conjugates and/or monoclonal antibodies, Prior allogeneic stem cell transplant at any time, Autologous stem cell transplant within 2 months of date of enrollment, High-dose cytotoxic chemotherapy (e.g., DCEP, KD-PACE, D-PACE) within 28 days of the enrollment date, Cytotoxic chemotherapy, such as cyclophosphamide, within 14 days of the enrollment date, Treatment with a PI, IMID, anti-CD38 antibody, or venetoclax within 7 days of the enrollment date, A cumulative dexamethasone dose of ≥ 100 mg within 14 days of the enrollment date, Radiation therapy within 7 days of the enrollment date

Any serious medical condition such as: Disabling neurological or psychiatric conditions, including altered mental status, dementia, or any condition that could preclude the use of high-dose steroids and/or accurate assessment of neurotoxicity, Any condition that could impair the ability of the subject to receive any of the study drugs

My myeloma can't be detected by standard tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis

Participants undergo apheresis to collect cells for CAR T-cell manufacturing

1 week

Bridging Therapy

Participants receive one cycle of talquetamab therapy as bridging therapy

4 weeks

Treatment

Participants receive lymphodepleting chemotherapy followed by Ciltacabtagene autoleucel infusion

1 week

Follow-up

Participants are monitored for safety and effectiveness after Ciltacabtagene autoleucel infusion

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ciltacabtagene Autoleucel
• Talquetamab

Trial Overview The study is testing talquetamab as a 'bridging therapy' before using ciltacabtagene autoleucel (cilta-cel) in those with difficult-to-treat multiple myeloma. It's an early-phase trial focusing on safety and how well this two-step treatment approach works.

How Is the Trial Designed?

Group I: Talquetamab and Ciltacabtagene autoleucel Experimental Treatment 2 Interventions

Participants with relapsed and/or refractory multiple myeloma (RRMM) will be administered talquetamab as a bridging therapy during CAR T-cell manufacturing and then receive Ciltacabtagene autoleucel CAR T-cell infusion after which they will be followed up to six months.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Citations

1. 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).

2. ashpublications.org ashpublications.org/blood/article/146/17/2063/546455/Sequential-targeting-in-multiple-myeloma

Sequential targeting in multiple myeloma: talquetamab, a ... Given its distinct target and high activity, short-term use of talquetamab as a bridging agent prior to BCMA CAR-T therapy may offer meaningful disease control.

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

Safety and activity of talquetamab in patients with relapsed ... Talquetamab is the first GPRC5D × CD3 bispecific antibody approved for relapsed or refractory multiple myeloma. In phase 1 of the ...

4. clinicaltrials.gov clinicaltrials.gov/show/NCT06550895

A Study of Ciltacabtagene Autoleucel and Talquetamab for ... The purpose of this study is to define the safety of Ciltacabtagene Autoleucel (Cilta-cel) and Talquetamab in participants with high-risk multiple myeloma ...

5. haematologica.org haematologica.org/article/view/haematol.2023.283931

Talquetamab in multiple myeloma Talquetamab, a bispecific antibody targeting GPRC5D and CD3, were reported in December of 2022 for the treatment of relapsed or refractory multiple myeloma.

6. ashpublications.org ashpublications.org/blood/article/145/1/85/518044/Safety-and-efficacy-of-standard-of-care

Safety and efficacy of standard-of-care ciltacabtagene ... Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes ...

7. ahdbonline.com ahdbonline.com/issues/2024/november-2024-vol-17-payers-guide/ongoing-analyses-and-recent-data-for-talvey-in-multiple-myeloma

Ongoing Analyses and Recent Data for Talvey in Multiple ... A study of ciltacabtagene autoleucel and talquetamab for the treatment of participants with high-risk multiple myeloma (MonumenTAL-8).