Combination Therapy for Multiple Myeloma

(MagnetisMM-20 Trial)

Recruiting at 47 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: BCMA-directed, CD47-SIRP alpha

Disqualifiers: Plasma cell leukemia, Cardiovascular diseases, others

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

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations to determine their safety for people with multiple myeloma, a type of blood cancer. It tests two combinations of medications: one with elranatamab (a type of immunotherapy), carfilzomib (also known as Kyprolis, a proteasome inhibitor), and dexamethasone, and the other with elranatamab and maplirpacept. The goal is to understand how these treatments work together and to identify the best doses. People who have undergone multiple myeloma treatments in the past, especially those who have tried three or more different therapies, might be suitable for this trial. Participants will receive the treatments in cycles over about two years. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive these new combinations.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that elranatamab, when used alone, can extend the lives of patients with multiple myeloma. Importantly, ongoing studies have not identified any new safety issues, meaning no unexpected side effects have emerged.

For those considering elranatamab with carfilzomib and dexamethasone, studies indicate that this combination effectively targets myeloma cells. Although these studies remain in the early stages, the combination appears promising and has not raised major safety concerns thus far.

Regarding the combination of elranatamab with maplirpacept, detailed safety information is not yet fully available. However, as this study is just beginning, researchers are closely monitoring and evaluating the treatment's safety.

Overall, these treatments are under study to ensure they are safe and manageable for people with multiple myeloma. Participants in these studies will contribute valuable information about the safety of these combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they introduce novel combinations that could offer new hope for patients. Elranatamab is a bispecific antibody that uniquely targets BCMA (B-cell maturation antigen), a promising target in multiple myeloma therapy. When combined with Carfilzomib, a proteasome inhibitor, and Dexamethasone, it has the potential to enhance treatment efficacy by attacking the cancer cells in different ways. Additionally, Maplirpacept, another experimental agent, is also being explored for its ability to potentially boost the immune response against myeloma cells. These innovative approaches aim to improve outcomes and provide alternatives to standard treatments like lenalidomide and bortezomib.

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

Research shows that elranatamab, one of the treatments studied in this trial, holds promise for treating multiple myeloma, a type of blood cancer. In earlier studies, 61% of patients with relapsed or hard-to-treat multiple myeloma experienced tumor reduction or remission. Carfilzomib, another treatment option in this trial, helps people with multiple myeloma live longer without disease progression. Specifically, patients treated with carfilzomib had a median progression-free period of 6.3 months. This trial evaluates both treatments for their effectiveness in addressing challenging cases of multiple myeloma, offering hope for those seeking new options. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for people with relapsed refractory multiple myeloma who've had prior treatments. Part 1 participants can have had 1-3 prior therapies and must not be pregnant, breastfeeding, or have used BCMA-directed therapy before. Part 2 requires at least 3 previous lines of treatment and no recent anti-BCMA or CD47-SIRP alpha-directed therapies (except CAR-T). All must meet specific disease measurement criteria and not have certain heart conditions or active infections.

Inclusion Criteria

I've had 1 to 3 treatments for my multiple myeloma, counting a stem cell transplant as one.

I previously responded well to carfilzomib, stopped it for reasons other than side effects, didn't relapse within 2 months after stopping, and it's been 6 months since my last dose.

Not pregnant or breastfeeding and willing to use contraception

Exclusion Criteria

I do not have any ongoing serious infections.

I had a stem cell transplant less than 3 months ago or I have ongoing graft versus host disease.

I have been treated with a BCMA-targeted therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive elranatamab in combination with carfilzomib and dexamethasone over 4-week cycles

4 weeks per cycle, up to 2 years

Weekly visits for IV infusions

Treatment Part 2A

Participants receive elranatamab in combination with maplirpacept over 4-week cycles

4 weeks per cycle, up to 2 years

Weekly visits for IV infusions

Treatment Part 2B

Participants receive randomized doses of elranatamab plus maplirpacept over 4-week cycles

4 weeks per cycle, up to 2 years

Weekly visits for IV infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Elranatamab

Trial Overview The study tests the safety of combining elranatamab with carfilzomib plus dexamethasone (Part 1) or maplirpacept (Part 2). It's divided into two parts: first to assess safety/tolerability of the combination treatments, second to find the best dose. Treatments are given in cycles over approximately two years, involving shots under the skin and IV infusions.

How Is the Trial Designed?

Group I: Part 2B Dose Randomization Experimental Treatment 2 Interventions

Randomized dose level Elranatamab plus Maplirpacept

Group II: Part 2A Dose Escalation Experimental Treatment 2 Interventions

Non randomized Elranatamab plus Maplirpacept

Group III: Part 1 Dose Escalation Experimental Treatment 2 Interventions

Non randomized Elranatamab plus Carfilzomib and Dexamethasone

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

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Carfilzomib is a highly effective proteasome inhibitor that has shown strong and lasting responses in patients with relapsed and refractory multiple myeloma, leading to its approval in the US.

Its favorable safety profile makes carfilzomib a promising candidate for combination therapies with other treatments, and ongoing Phase III studies are evaluating its efficacy and safety in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of carfilzomib combination therapy in the management of multiple myeloma. Moreau, P.[2014]

In a phase 1b study involving patients with newly diagnosed multiple myeloma, the combination of carfilzomib, cyclophosphamide, and dexamethasone showed an impressive overall response rate of 87.5% at the highest carfilzomib dose of 56 mg/m2.

The treatment was generally well-tolerated, with manageable adverse effects; however, some patients experienced grade 3 or higher toxicities, including anemia and neutropenia, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2). Boccia, RV., Bessudo, A., Agajanian, R., et al.[2018]

Carfilzomib significantly improves progression-free survival, overall survival, and overall response rate in patients with relapsed/refractory multiple myeloma, based on evidence from 14 systematic reviews involving moderate quality data.

However, treatment with carfilzomib is associated with increased risks of cardiovascular events, nephrotoxicity, and serious infections, highlighting the need for careful monitoring and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews. Georgoulis, V., Haidich, AB., Bougioukas, KI., et al.[2022]

Carfilzomib, when used in combination with lenalidomide and dexamethasone, significantly prolongs progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma, based on results from the phase III ASPIRE study involving a multinational patient population.

The combination therapy has a manageable safety profile, with low incidences of severe adverse events, suggesting it is a viable treatment option for patients who have received prior therapies, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. Hoy, SM.[2018]

Carfilzomib, a proteasome inhibitor approved for relapsing multiple myeloma, was associated with a case of fatal pulmonary toxicity in a 61-year-old male patient, highlighting a potential serious side effect of the drug.

The patient developed acute respiratory distress syndrome and diffuse alveolar hemorrhage shortly after starting carfilzomib, suggesting a direct link between the medication and the severe lung complications, which had not been previously reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal pulmonary toxicity due to carfilzomib (Kyprolis™). Lataifeh, AR., Nusair, A.[2020]

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]

In a multicenter study of 85 patients with relapsed/refractory multiple myeloma, the KRd combination (Carfilzomib, lenalidomide, and dexamethasone) showed a high overall response rate of 95% and a median progression-free survival of 36 months after a median follow-up of 40 months.

The KRd regimen was found to be safe, with a low discontinuation rate of 6% due to toxicities, and most adverse events were mild, confirming its feasibility in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone in relapsed refractory multiple myeloma: a prospective real-life experience of the Regional Tuscan Myeloma Network. Antonioli, E., Pilerci, S., Attucci, I., et al.[2023]

Carfilzomib-containing combinations as frontline therapy for multiple myeloma showed a high overall response rate of 94% and a complete response rate of 21% across 13 trials involving 704 subjects.

The combination of carfilzomib with lenalidomide and dexamethasone (CFZ-LEN-DEX) resulted in a significantly higher complete response rate of 49% compared to other combinations, indicating it may be the most effective regimen for newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials. Sheng, Z., Li, G., Li, B., et al.[2018]

In patients with mild to moderate hepatic impairment, carfilzomib showed approximately 20-50% higher drug exposure compared to those with normal liver function, but this increase is not expected to be clinically significant due to the drug's pharmacokinetic variability.

The safety profile of carfilzomib in patients with advanced solid tumors was consistent with previous findings, although there was a noted increase in adverse events related to liver function abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study. Brown, J., Plummer, R., Bauer, TM., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9713064/

Carfilzomib usage patterns and outcomes in patients with ... Median progression‐free survival for the overall cohort was 6.3 months with overall survival 19.7 months. This study provides a benchmark for carfilzomib‐based ...

2. kyprolis.com kyprolis.com/treatment-results

Efficacy | KYPROLIS® (carfilzomib) KYPROLIS helps people with relapsed or refractory multiple myeloma live longer without their disease getting worse and reach a complete response.

3. nature.com nature.com/articles/s41408-025-01256-2

Carfilzomib prescribing patterns and outcomes for relapsed ... Our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of ...

4. kyprolis-hcp.com kyprolis-hcp.com/combinations/kd-efficacy

Kd Efficacy | KYPROLIS® (carfilzomib) Phase 3, randomized, open-label superiority study: (N=929) comparing Kd 56 mg/m 2 twice weekly to Vd in relapsed or refractory multiple myeloma patients.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001533

Original Study Real-World Use of carfilzomib-lenalidomide ... Carfilzomib administered as either KRd or Kd was effective and well tolerated, even in patients with multiple prior LOTs, confirming the safety and response ...

6. elrexfio.com elrexfio.com/results

ELREXFIO® (elranatamab-bcmm) Results | Safety Info In Group A, results with ELREXFIO showed: 26% of people had a CR or better: Multiple myeloma could not be detected in the blood or urine after treatment. 26% of ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40713551/

Comparison of outcomes with elranatamab and real world ... Clinical outcomes in the ECA were poor (median PFS 3.71 months [95% confidence interval (CI) 2.73-4.73], median OS 11.00 months [8.02-18.10]).

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7549

A US subgroup analysis from MagnetisMM-3. The ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of ELRA in patients (pts) with RRMM and no prior BCMA-directed ...

9. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14624-9

Comparison of outcomes with elranatamab and real world ... This study aimed to characterise outcomes for real world TCE RRMM patients and to estimate the treatment effect of elranatamab compared to ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11269363/

Long‐term survival and safety of elranatamab in patients with ... Elranatamab monotherapy continues to improve survival outcomes without new safety signals. ... multiple myeloma: phase 2 MagnetisMM‐3 trial results. Nat Med. 2023 ...