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Phase I/II LINKER-MM1 Trial Data Show Depth of Response with Linvoseltamab for Relapsed/Refractory Multiple Myeloma

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Results from the pivotal Phase I/II LINKER-MM1 trial (NCT03761108) show the long-term efficacy of linvoseltamab for the treatment of patients with relapsed/refractory (R/R) multiple myeloma (MM).1 These findings, presented at the European Hematology Association Congress 2024 and published by the Journal of Clinical Oncology, demonstrated a growing depth of response and durability with the investigational therapy.1,2

“Previous results from LINKER-MM1 have demonstrated that linvoseltamab has compelling efficacy characterized by deep and durable responses. With 14-months of median follow-up, 50% of patients achieved a complete response or better, despite their cancer being refractory to or relapsing on standard therapies,” Suzanne Lentzsch, MD, PhD, director of the Multiple Myeloma and Amyloidosis Program at Columbia University, said in a press release. “Additionally, a study using US-based electronic health record data to indirectly compare linvoseltamab to real-world standard-of-care treatment also support the overall body of evidence for this investigational medicine in heavily pretreated multiple myeloma. Collectively, these presentations underscore the exciting potential of linvoseltamab as we await decisions from regulatory authorities.”1

In February, the FDA granted Priority Review to linvoseltamab for adults with RRMM who experienced disease progression following prior administration of at least three therapies.3

Linvoseltamab is a bispecific antibody designed to bridge B-cell maturation antigen on multiple myeloma cells that have CD3-expressing T cells, which subsequently activates T cells to enduce the killing of cancer cells. The FDA assigned the application with a Prescription Drug User Fee Act date of August 22, 2024.

An estimated 35,000 US residents will be diagnosed with multiple myeloma on an annual basis. Although research efforts have achieved significant progress in treating multiple myeloma, the disease is not yet curable. Current treatments have been able to inhibit disease progression; however, most patients will require additional therapies as their disease progresses.3

The open-label, multicenter, dose-escalation and expansion LINKER-MM1 trial is analyzing linvoseltamab in 282 patients with RRMM.2 The Phase I dose-escalation part of LINKER-MM1 primarily analyzed the drug’s safety, tolerability, and dose-limiting toxicities across nine dosing levels with varying administration regimens. Phase II has a primary endpoint of objective response rate (ORR), with key secondary endpoints that include duration of response (DOR), progression-free survival (PFS), minimal residual disease negativity rate, and overall survival (OS).

At the 14-month median follow-up point in patients administered the 200 mg dose (N=117), the findings reinforced the durability and growing depth of response shown in prior research of linvoseltamab. For the primary endpoint, the linvoseltamab cohort had a 71% ORR, with 50% of patients showing a complete response (CR) or better and 63% showing a very good partial response (PR) or better, as determined by an independent review committee.

Median DoR was 29 months among all responders, whereas median DoR was not reached for patients who showed a CR or better. Among all patients and in those who experienced a CR or better, investigators reported an 81% and 95% estimated probability of maintaining a response at 12 months, respectively, after experiencing a PR or better.

Median PFS was not reached in the trial, with the data showing 70% estimated probability of being progression free at 12 months among all patients. The estimated probability of being progression free was 96% among patients experiencing a CR or better.

Median OS was 31 months for all patients (95% CI: 22 months to NE) and median OS was not reached for those experiencing a CR or better. Among all patients and in those experiencing a CR or better, investigators reported a 75% and 100% estimated probability of survival at 12 months, respectively.

In terms of safety, 14-month median follow-up findings were consistent with what was reported at the 11-month median follow-up. The most frequently reported treatment-emergent adverse event (TEAE) was cytokine release syndrome, which was reported in 46% of patients.

Infections were reported in 74% of patients, 36% of which were grade 3 or 4, but the frequency and severity of the infections decreased after six months. The most frequently reported grade 3 or 4 TEAEs (≥20%) were neutropenia (42%) and anemia (31%). There were six deaths associated with TEAEs that occurred during treatment or within 30 days of the last treatment dose. Five of the deaths resulted from infection and one from renal failure.

References

1. Updated Linvoseltamab Data Showcase Continued Deepening of Responses in Patients With Heavily Pre-Treated Multiple Myeloma. News release. Regeneron. June 16, 2024. Accessed June 17, 2024. https://investor.regeneron.com/news-releases/news-release-details/updated-linvoseltamab-data-showcase-continued-deepening

2. Bumma N, et al. Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma. Journal of Clinical Oncology. June 16, 2024. doi.org/10.1200/JCO.24.010

3. Linvoseltamab BLA for treatment of relapsed/refractory multiple myeloma accepted for FDA priority review. News Release. Regeneron. February 21, 2024. Accessed June 17, 2024. https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-bla-treatment-relapsedrefractory-multiple-myeloma