Rafael Fonseca, MD, Reviews Ongoing MagnestisMM-9 Trial of Elranatamab in Relapsed Multiple Myeloma

Rafael Fonseca, MD, director for Innovation and Transformational Relationships at the Mayo Clinic’s campus in Phoenix, Arizona

Elranatamab is an investigations therapy that is currently being analyzed in the phase 2 MagnestisMM-9 trial (NCT05014412) for patients with relapsed/refractory multiple myeloma.¹ At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, a poster was presented outlining the study design and objectives. The main objective of this trial is to evaluate the safety, specifically the rate of grade 2 cytokine release syndrome (CRS) in patients receiving the bispecific antibody. Investigators plan to reduce CRS by using premedication and a 2 step-up priming dose regimen initiated within the first week of treatment.

Rafael Fonseca, MD, director for Innovation and Transformational Relationships at the Mayo Clinic’s campus in Phoenix, Arizona, and lead investigator of this trial, spoke with CancerNetwork® about the MagnestisMM-9 trialongoing study. During the interview, Fonseca discusses how elranatamab is being used in trial subjects, the study design, and what the next steps are when the trial is completed following trial completion will be.

CancerNetwork^®: How is elranatamab being used in this trial to treat multiple myeloma?

Fonseca: The poster we presented [at ASCO] was a trial in progress, which is a clinical trial named MagnetisMM-9. It is a trial which addresses the role of elranatamab. Elranatamab is a bispecific antibody that will be used, we hope, for the treatment of patients with multiple myeloma in the relapsed and refractory setting. It targets BCMA [Bb-cell maturation agentsantigen]., Llike other bispecifics, it that engages the T cells. We know from theMagnetisMM-1 clinical trial [NCT03269136]that was reported by Alexander M. Lesokhin, MD, that this compound shows activity against multiple myeloma.²The idea behind the trial is to find the best way to use this new compound. What we’re doing in this trial, the primary endpoint is to mitigate CRS.

What methods were used to conduct this trial?

The study will have 2 phases and in 1 of the phases we’re involves increasing doses of elranatamab with priming, hopefully, to ameliorate CRS. This includes not only the pre-medications, but also the priming strategies. F from the time that the patients receives what we think will be athe therapeutic dose, there’s less of a lower risk of CRS [occurring]. That would be number 1. Ultimately, [we want to] determine what would it be athe recommended phase 2 dose based on this clinical trial. The second part of it is how to space out the infusions. Currently, patients are being treated on a weekly basis, and over time, they can be expanded to every other week. But if you get a higher dose, could you be able to give this every other week? This is a factor of major convenience for patients.

How does this treatment fit into the current treatment landscape?

The advent of bispecific antibodies is dramatically changing in how we start to think about the treatment of multiple myeloma. We’ve been very lucky to have 2 CAR T-cell therapies approved [for multiple myeloma] by the FDA over the past year and a half, but t. This is still is not sufficient. There are’s some challenges with CAR T-cell therapys because you have to manufacture the product, and you have to re-infuse the cells. There’s somewhat limited access right now. Everyone is excited about the idea of having an off-the-shelf product, something where I could see in[that allows us to see] the patient in the morning, and then in the afternoon, the patient could be receiving the treatment. It’s going to be interesting to see how that plays out. We have incredible results with some of the CAR T-cell therapies. If you look at the data with cilta-cel [ciltacabtagene autoleucel; Carvykti], most patients respond. The reality is [that this therapy is] not available for all patients and under because of certain complexities and the time it takes to get the product manufactured and then re-infused back to the patient, which makes the bispecifics attractive.

As this is a trial in progress, what do you see as the next steps being if the results are positive?

The next steps for the testing of elranatamab and likewise other bispecific antibodies will be for their introduction earlier in the course of the disease. I for one, am interested in the idea of having patients receive some form of induction therapy, after which we do a very thorough assessment, including the determination of MRD [minimal residual disease]. For those patients that who are MRD positive, the idea would be that you consolidate what you[using the treatment used] did initially. I would love to see that, but right now we are in the first phases. We’re treating patients who have active and aggressive disease, but I would love to see, just like it's been planned forwith CAR T-cell therapies,s that bispecifics become part of the first-line therapy. The reality is that possibilities for a cure and durable control of myeloma exist primarily in the first line of therapy, so t. That’s where we have to optimize it all. I know, it's[This is] several steps ahead, but we’ve seen similar developments in the field of ALL [acute lymphoblastic leukemia] that where investigators people are using bispecifics as far as therapy for some of the subsets of ALL.

What do you hope your colleagues took take away from this presentation?

At this point, because we still don’t have the results, and it’s more of a mitigation strategy for CRS I hope it’s just 1 more example of how the development of this type of compound becomes another piece ofbrings hope for to our patients. We have another trial already being presented to the FDA for a bipecific [antibodyies] and we’re hoping that there will be more submissions so that if the field moves forward, it’s there’s going to be somewhat fierce competition to get some of the agent’s positioned as the next line of therapy for myeloma. There are no bispecifics that are approved as of yet.

References

1. Fonseca R, Kuroda J, Ishida, et al. MagnetisMM-9: An open-label, multicenter, non-randomized phase 1/2 study of elranatamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2022;40(suppl 16):TPS8068. doi:10.1200/JCO.2022.40.16_suppl.TPS8068
2. Jakubowiak AJ, Bahlis NJ, Raje NS, et al. Elranatamab, a BCMA-targeted T-cell redirecting immunotherapy, for patients with relapsed or refractory multiple myeloma: Updated results from MagnetisMM-1. J Clin Oncol. 2022;40(suppl 16):8014. doi:10.1200/JCO.2022.40.16_suppl.8014