Talquetamab + Teclistamab for Multiple Myeloma

(ROTATE Trial)

Overseen By Carole Ramm

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Noffar Bar

Must be taking: Anti-CD38 antibodies

Must not be taking: Monoclonal antibodies, Cytotoxic, PI, IMiD

Disqualifiers: HIV, Hepatitis B/C, Heart failure, 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

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, talquetamab and teclistamab, for multiple myeloma, a type of blood cancer that often recurs after treatment. The researchers aim to determine if these treatments can eliminate leftover cancer cells after initial therapy, potentially improving patient outcomes. Participants will first receive talquetamab; if it fails to sufficiently reduce cancer cells, they will switch to teclistamab. Those recently treated for multiple myeloma who still have residual cancer cells might be suitable for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from innovative therapies.

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

The trial information does not specify if you need to stop taking your current medications. However, there are restrictions on recent treatments like targeted therapy, monoclonal antibody therapy, and others within certain timeframes before joining the trial. It's best to discuss your current medications with the trial team to ensure eligibility.

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

Research has shown that talquetamab and teclistamab are generally well-tolerated by patients with multiple myeloma, a type of blood cancer. In earlier studies, patients whose cancer returned or didn't respond to other treatments experienced positive outcomes with these medications. The safety profile of using talquetamab and teclistamab together is similar to using each drug individually.

Talquetamab has received fast-track approval from the FDA, indicating an acceptable level of safety in past research. This suggests these treatments are safe enough for further testing in clinical trials. However, all medications can have side effects. While studies have not identified any unexpected safety issues, consulting a healthcare provider is advisable for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Talquetamab and Teclistamab for treating multiple myeloma because these drugs introduce a novel approach by using bispecific antibodies. Unlike standard treatments that typically focus on chemotherapy or proteasome inhibitors, Talquetamab targets GPRC5D and Teclistamab targets BCMA, both of which are specific proteins found on multiple myeloma cells. This dual targeting approach is designed to more precisely attack cancer cells while sparing healthy cells, potentially leading to fewer side effects and improved effectiveness. Additionally, both treatments are administered subcutaneously, which can offer a more convenient and less invasive option compared to traditional intravenous therapies.

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

This trial will evaluate the combination of talquetamab and teclistamab for treating multiple myeloma. Studies have shown that using these drugs together looks promising, especially for patients whose disease has returned or not responded to other treatments. This combination has led to better results, with researchers observing that patients lived without their disease worsening for an average of 15.4 months, compared to less than 3 months with standard treatments. In one study, 61.1% of patients showed improvement, and 33.3% had no detectable disease. These drugs target specific proteins on cancer cells, helping the immune system attack and destroy the cancer more effectively. Overall, early research suggests this combination could be a major step forward for patients with multiple myeloma. ^{2 3 5 6 7}

Who Is on the Research Team?

Noffar Bar, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with multiple myeloma who still have minimal residual disease (MRD) after initial treatment. It's aimed at those who haven't reached MRD negativity, which means there are still cancer cells detectable even after therapy.

Inclusion Criteria

Must not be progressing as per IMWG criteria

Provision of signed and dated ICF

I am 18 years old or older.

Exclusion Criteria

My heart condition is severe.

Known history, virologic, or serological evidence of hepatitis B or C virus (HBV/HCV) infection

I do not have an active or suspected infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation Treatment

Participants receive consolidation treatment with GPRC5D-targeted bispecific talquetamab. If MRD negativity is not achieved, switch to B-cell maturation antigen TCE, teclistamab.

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Safety follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Talquetamab
• Teclistamab

Trial Overview The study tests talquetamab as a consolidation therapy to reduce malignant plasma cells and achieve MRD negativity in patients. If unsuccessful, it switches to teclistamab. The goal is to improve patient outcomes by increasing rates of MRD negativity over a period of up to one year.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 2 Interventions

Talquetamab is a GPRC5DxCD3 bispecific antibody. It is supplied as a sterile, preservative-free solution for subcutaneous administration. Teclistamab is a BCMAxCD3 bispecific antibody. It is supplied as a sterile, preservative-free solution for subcutaneous administration.

Who Is Running the Clinical Trial?

Noffar Bar

Lead Sponsor

Johnson & Johnson

Industry Sponsor

Trials

116

Recruited

167,000+

Citations

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

Talquetamab Plus Teclistamab Effective for Relapsed or ... Many patients with relapsed or refractory (R/R) multiple myeloma (MM) benefitted from treatment with a combination of talquetamab plus teclistamab.

2. 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 ... The median PFS reached 15.4 months, which is amazing, because standard therapy yields a median PFS of less than 3 months, and even the approved ...

3. hematologyadvisor.com hematologyadvisor.com/reports/multiple-myeloma-rrmm-talquetamab-teclistamab-big-step-forward-treatment/

Talquetamab Plus Teclistamab Is “Big Step Forward” for ... Researchers determined combination talquetamab and teclistamab demonstrated promising efficacy results for patients with RRMM and EMD.

4. jnj.com jnj.com/media-center/press-releases/novel-combination-of-talvey-talquetamab-tgvs-and-tecvayli-teclistamab-cqyv-suggests-high-response-rates-and-durable-responses-in-triple-class-refractory-patients-with-relapsed-or-refractory-multiple-myeloma-including-those-with-extramedullary-disease

Novel combination of TALVEY® (talquetamab-tgvs) and ... At the RP2R (n=18), results showed an ORR of 61.1 percent, with CR+ rate of 33.3 percent, an 18-month DOR of 81.8 percent, and an 18-month PFS ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11979001/

Real-world treatment patterns for teclistamab and ... Real-world treatment patterns for teclistamab and talquetamab in multiple myeloma (MM): experience from 609 patients

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

Safety and activity of talquetamab in patients with relapsed ... Talquetamab continued to demonstrate high overall response rates in heavily pretreated patients with relapsed or refractory multiple myeloma ...

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... In August 2023, the FDA granted accelerated approval to talquetamab, based on the impressive efficacy and safety results of the MonumenTAL‐1 ...