Teclistamab vs. PVd/Kd for Multiple Myeloma

(MajesTEC-9 Trial)

Not currently recruiting at 324 trial locations

Overseen By SparkCures Patient Support (US only)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Anti-CD38 antibodies, Lenalidomide

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: BCMA therapy, CNS involvement, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 aims to evaluate the effectiveness of a new treatment called teclistamab for people with multiple myeloma, a type of blood cancer that has returned or isn't responding to treatment. In one part of the trial, participants will receive teclistamab alone, while another group will receive a combination of existing drugs such as bortezomib, carfilzomib, pomalidomide, and dexamethasone. The trial seeks participants whose multiple myeloma has returned after 1 to 3 previous treatments and who show signs of worsening. This study will help researchers determine if teclistamab could offer a better treatment option for this challenging condition. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you've recently taken certain medications like strong CYP3A4 inducers or have received a live vaccine within 4 weeks before randomization.

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

A previous study found teclistamab to be safe for patients with multiple myeloma, with manageable side effects. Common side effects included low blood cell counts and mild to moderate infections, which most patients managed well.

Research has shown that combining pomalidomide, bortezomib, and dexamethasone, as well as carfilzomib and dexamethasone, is generally safe for patients with multiple myeloma. Studies found these treatments can cause side effects like tiredness and low blood counts, but these are usually manageable.

Both teclistamab and these drug combinations have demonstrated safety in earlier trials. Participants in this trial can expect similar side effects, based on past studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about teclistamab for multiple myeloma because it works differently from most current treatments. While standard options like bortezomib or carfilzomib target the cancer cells directly, teclistamab is a bispecific antibody that simultaneously binds to cancer cells and T-cells, which are part of the immune system. This dual action helps the immune system recognize and attack the cancer cells more effectively, offering a new approach that could enhance treatment outcomes. Additionally, teclistamab's novel mechanism of action represents a promising advancement in immunotherapy, aiming to harness the body's own defenses to fight multiple myeloma.

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

In this trial, participants will receive either teclistamab or a combination treatment of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Research shows that teclistamab may help treat relapsed or hard-to-treat multiple myeloma, with studies finding that 63% of patients responded to this treatment. Teclistamab can also aid those who haven't succeeded with other BCMA-targeted treatments.

The combination treatments using PVd or Kd are also effective for multiple myeloma. Pomalidomide is approved for patients who have undergone several treatments, and research has shown these combinations to be helpful in managing the disease. Both approaches in this trial offer options for those facing this challenging condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for people with multiple myeloma who've had 1-3 prior treatments but didn't respond well or their disease got worse. They must meet specific criteria for measurable disease, be able to follow the study's lifestyle rules, not be pregnant or breastfeeding, and have a decent ability to perform daily activities (ECOG score of 0-2). People can't join if they've had BCMA-targeted therapy before, certain allergies or conditions like CNS involvement in their cancer, recent live vaccines, or other specific blood disorders.

Inclusion Criteria

My last cancer treatment did not work as expected.

I have been diagnosed with multiple myeloma according to international standards.

I have had 1-3 treatments for myeloma, including specific ones.

Exclusion Criteria

I have received treatment targeting BCMA before.

I meet the specific requirements for control therapies, including no major allergies or neuropathy.

I have a specific blood disorder like Waldenstrom's or POEMS syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive either teclistamab monotherapy or PVd/Kd based on the principal investigator's choice

Up to 9 years

Treatment Part 2

Participants receive an alternative dosing regimen of teclistamab

Up to 9 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 9 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Carfilzomib
• Dexamethasone
• Pomalidomide
• Teclistamab

Trial Overview The study aims to see how effective Teclistamab alone is compared to two other treatment combinations: Pomalidomide with Bortezomib and Dexamethasone (PVd), or Carfilzomib with Dexamethasone (Kd) in treating relapsed/refractory multiple myeloma. Participants will receive one of these therapies based on random assignment.

How Is the Trial Designed?

Group I: Teclistamab Experimental Treatment 1 Intervention

Participants will receive teclistamab monotherapy in Part 1 and an alternative dosing regimen of teclistamab in Part 2.

Group II: Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd) Experimental Treatment 4 Interventions

Participants will receive either PVd or Kd based on principal investigator's choice during Part 1 of the study.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead 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

In the ENDURANCE trial involving patients with newly diagnosed multiple myeloma, the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) did not improve progression-free survival compared to the standard treatment of bortezomib, lenalidomide, and dexamethasone (VRd).

These findings suggest that KRd may not be a more effective treatment option than the current standard of care for patients with NDMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triplet Fails to Induce Superior PFS in Newly Diagnosed Multiple Myeloma. Skarzynski, J.[2021]

Carfilzomib is an effective treatment for patients with relapsed or refractory multiple myeloma, as shown in the PX-171-003-A1 phase II trial, which involved patients who had already undergone at least two prior therapies.

Common side effects of carfilzomib include fatigue, anemia, nausea, and thrombocytopenia, and it is recommended to use dexamethasone as premedication to reduce the risk of infusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib: A new proteasome inhibitor for relapsed or refractory multiple myeloma. Steele, JM.[2014]

The novel combination therapy of carfilzomib, pomalidomide, and dexamethasone (CPD) was found to be well-tolerated and highly active in treating patients with relapsed and refractory multiple myeloma, with a total of 32 patients enrolled in the study.

The maximum tolerated dose (MTD) was established at carfilzomib 20/27 mg/m², pomalidomide 4 mg, and dexamethasone 40 mg, although hematologic adverse events were common, affecting over 60% of patients, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Shah, JJ., Stadtmauer, EA., Abonour, R., et al.[2022]

The MUK Five trial is a phase II study comparing the effectiveness of a new combination treatment (carfilzomib, cyclophosphamide, and dexamethasone) against the standard treatment (cyclophosphamide, bortezomib, and dexamethasone) in patients with multiple myeloma at first relapse, involving participants who have received no more than one prior treatment.

The trial aims to determine if the new combination (CCD) is at least as effective as the standard treatment (CVD) in achieving significant response rates, while also assessing the potential benefits of maintenance therapy with carfilzomib for improving progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. Brown, S., Hinsley, S., Ballesteros, M., et al.[2022]

In a study of 85 newly diagnosed multiple myeloma patients, a high-dose bortezomib regimen (1.6 mg/m2) resulted in a significantly higher complete response rate (43.6%) compared to a low-dose regimen (1.3 mg/m2) which had a response rate of only 12.8%.

While the high-dose regimen showed improved efficacy, particularly in younger patients and those with advanced disease, it was associated with a higher incidence of severe diarrhea, leading to more dose reductions in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. Li, F., Yao, FS., Zhu, XJ., et al.[2021]

Cefepime combined with zidebactam (FEP-ZID) demonstrated a broad and potent in vitro activity against multidrug-resistant (MDR) bacteria, including challenging strains of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

FEP-ZID was effective against various carbapenemase-producing bacteria and P. aeruginosa with multiple resistance mechanisms, suggesting it could be a promising treatment option for severe infections caused by these resistant pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens. Thomson, KS., AbdelGhani, S., Snyder, JW., et al.[2020]

Cefpirome, a new fourth-generation cephalosporin, demonstrated excellent antibacterial activity against a wide range of pathogens, including Enterobacteriaceae and Streptococcus pneumoniae, with low minimum inhibitory concentrations (MIC90) indicating strong efficacy.

Compared to third-generation cephalosporins, cefpirome showed superior effectiveness against certain resistant strains, such as cephalosporinase-depressed mutants of Enterobacter cloacae, highlighting its potential as a more effective treatment option in intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of cefpirome against microorganisms isolated in haematology, oncology and intensive care units in Switzerland. Liassine, N., Bille, J., Breer, C., et al.[2023]

New combination antibiotics like ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam, and meropenem/vaborbactam show similar clinical success rates compared to older therapies for treating various infections, based on a review of 25 studies.

However, these new antibiotics demonstrate significantly better clinical success in patients with carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDRPA) infections, suggesting they may be more effective for these specific drug-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the clinical effectiveness of new beta-lactam/beta-lactamase inhibitor combination antibiotics: A systematic literature review and meta-analysis. Wilson, GM., Fitzpatrick, MA., Walding, K., et al.[2023]

Ceftazidime/avibactam and meropenem/vaborbactam are effective against KPC-producing Klebsiella pneumoniae, with ceftazidime/avibactam showing synergy when combined with colistin, regardless of the ompK36 genotype.

The presence of porin mutations in KPC-Kp can reduce the effectiveness of ceftazidime/avibactam combinations, while some combinations with meropenem/vaborbactam showed enhanced killing activity, indicating the importance of understanding genetic variations in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutations in ompK36 differentially impact in vitro synergy of meropenem/vaborbactam and ceftazidime/avibactam in combination with other antibiotics against KPC-producing Klebsiella pneumoniae. Rogers, TM., Kline, EG., Griffith, MP., et al.[2023]

The KD-PACE regimen, which includes carfilzomib instead of bortezomib, was found to be a feasible bridging therapy for 52 patients with relapsed or refractory multiple myeloma, showing no unexpected toxicities.

Patients who were successfully bridged to autologous or allogenic stem cell transplants or clinical trials had significantly better progression-free survival (8.3 months) and overall survival (16.7 months) compared to those who were not bridged (2.3 months and 4.3 months, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma, Plasma Cell Leukemia and Extramedullary Myeloma. Alsouqi, A., Khan, M., Dhakal, B., et al.[2022]

In a phase II study involving 98 patients with untreated multiple myeloma, both the bortezomib-thalidomide-dexamethasone (VTD) and the cyclophosphamide-added regimen (VTDC) showed high rates of near-complete response (nCR) or better, with 51% and 44% respectively, indicating both regimens are effective induction therapies.

However, the addition of cyclophosphamide in VTDC led to increased toxicity, with higher rates of grade 3 to 4 adverse events (57% vs 47% for VTD) and no significant improvement in treatment efficacy, suggesting that VTD may be the safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. Ludwig, H., Viterbo, L., Greil, R., et al.[2022]

Four new agents have been approved for treating relapsed/refractory multiple myeloma, including bortezomib, lenalidomide, thalidomide, and liposomal doxorubicin, but there is no standard treatment, making personalized therapy essential.

New agents like carfilzomib and pomalidomide are being studied for their effectiveness and side effects, highlighting the importance of understanding treatment-related adverse events in choosing the best therapy for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. Vij, R.[2017]

Carfilzomib, a recently approved treatment for relapsed and refractory multiple myeloma, has a distinct hematologic safety profile compared to other treatments, which are often associated with higher rates of anemia, neutropenia, and thrombocytopenia.

The article reviews data from four phase II studies to assess the hematologic adverse events related to carfilzomib and provides recommendations for managing these events, highlighting its potential as a safer option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of hematologic adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib. Nooka, AK.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10039009/

Efficacy and safety of pomalidomide, bortezomib ... Pomalidomide is currently approved for relapsed-refractory multiple myeloma. This single-arm, open-label, phase 2 study was the prospective ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571914/

Efficacy and Safety of Daratumumab, Pomalidomide ... Daratumumab-based combinations with pomalidomide/dexamethasone (DPd), or bortezomib/dexamethasone (DVd), have shown activity in relapsed/ ...

3. myeloma.org myeloma.org/velcade-bortezomib

Velcade (Bortezomib) & Multiple Myeloma Treatment | IMF In the XVd group, the doses of Velcade and dexamethasone were reduced by 40% and 25%, respectively. At the median follow-up of 16.5 months in the Vd group ...

4. myeloma.org myeloma.org/pomalyst-pomalidomide

Pomalyst (Pomalidomide) for Multiple Myeloma | The IMF Pomalyst is indicated for the treatment of adult patients with relapsed and refractory myeloma who have received at least 2 prior therapies.

5. nature.com nature.com/articles/s41375-020-01021-3

outcomes by prior treatment at first relapse | Leukemia These data demonstrate the benefit of PVd at first relapse, including immediately after upfront lenalidomide treatment failure and other common first-line ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4643003/

Carfilzomib, pomalidomide, and dexamethasone for ... Results suggest that the regimen is a well-tolerated and highly active combination for patients with relapsed/refractory multiple myeloma. Abstract. Treatment ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36964143/

Efficacy and safety of pomalidomide, bortezomib ... Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had ISS- ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01734928

NCT01734928 | Safety and Efficacy of Pomalidomide ... The purpose of this study is to compare the efficacy of the combination of pomalidomide, bortezomib and low dose dexamethasone to the combination of bortezomib ...

9. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)02886-1/fulltext

Efficacy and Safety of Daratumumab, Pomalidomide and ... Among 399 patients, progression-free and overall survival outcomes were similar between groups, with DPd more frequently associated with ...

10. nature.com nature.com/articles/s41408-023-00816-8

Efficacy and safety of pomalidomide, bortezomib ... Outcomes of patients with multiple myeloma ... pomalidomide, and dexamethasone is safe and efficacious in newly diagnosed multiple myeloma.