Amgen's AMG 420 Finds Early Success in Patients With Relapsing/Refractory Multiple Myeloma

Amgen’s pipeline drug AMG 420, a bispecific T-cell engager (BiTE) for the treatment of patients with relapsing/refractory multiple myeloma (RRMM), has found positive preliminary results in a phase 1 trial. The development of AMG 420 adds another contender into the immunotherapy podium for treating MM.

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Back in 2016, Amgen bought the BiTE platform from Boehringer Ingelheim.¹ The idea of BiTE in combating cancer is to specifically direct T cells to destroy cancer cells. BiTE is composed of 2 single chain antibodies, with 1 antibody specific for B-cell maturation antigen (BCMA), a tumor antigen, and the other specific for CD3, a protein found on the surface of T cells. By binding to both BCMA and CD3, BiTE technology forms a structure similar to a bridge between the T cell and tumor cell, allowing the T cell to target the tumor cell, resulting in tumor cell lysis, reduced tumor burden, and halting the progression of the cancer.^1-3

In the 2018 myeloma meeting, Amgen’s pipeline drug AMG 420, an anti-BCMA BiTE product, was considered to have potential beneficial effects in patients with RRMM. Preliminary results were reviewed, and findings showed that 5 patients on AMG 420 were able to obtain stringent complete responses, with 4 of the 5 patients having negative minimal residual disease exceeding 10 months.² AMG 420 is still in phase 1 trials, but the positive results may streamline AMG 420 ahead into future clinical trials.

Another drug that has entered the MM drug development market is bb2121, an anti-BCMA chimeric antigen receptor (CAR) T drug developed by Celgene with bluebird bio, also designed to treat patients with RRMM. Although created to target the same population as AMG 420, bb2121 is a gene therapy. T cells extracted from a patient’s own white blood cells are collected and genetically modified to recognize BCMA. They are then returned to a patient’s body where they target MM tumor cells that express the BCMA.⁴

Results from phase 1 study of bb2121 were revealed at the annual meeting of the American Society of Clinical Oncology in June this year. The overall response rate in the 18 patients with RRMM was 94%, with 56% of the patients having complete response. Nine of the 10 patients were also MRD-negative. At 40 weeks, the median duration of response and progression-free survival were not reached.⁵ Currently, bb2121 is in phase 2/3 trials, where Celgene and bluebird bio had begun testing the efficacy and safety of bb2121 and comparing it with other treatment options for MM (NCT03361748, NCT0365112).

Right now, there is reason to believe that AMG 420 may have similar efficacy to bb2121 for treating patients with RRMM. However, this assumption will only be verified once the results of longer-term data is available. The development of these new drugs in the field of MM is groundbreaking, and it will be very interesting to see where these drugs will fit within MM treatment guidelines.

References

1. AMG 420. Immuno-oncology News website. immuno-oncologynews.com/amg-420/. Accessed September 19, 2018.

2. Chrisomalis T. Amgen looks to enter multiple myeloma space: can it compete? Seeking Alpha website. seekingalpha.com/article/4205437-amgen-looks-enter-multiple-myeloma-space-can-compete. Updated September 10, 2018. Accessed September 19, 2018.

3. Amgen Oncology. BiTE: engage the immune system. www.biteantibodies.com/. Accessed September 19, 2018.

4. Bb2121. Imnuno-oncology News website. immuno-oncologynews.com/bb2121/. Accessed September 19, 2018.

5. Noopur RS, Berdeja JG, Lin Y, et al. bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: updated results from a multicenter phase 1 study. Presented at: the 2018 Annual meeting of the American Society of Clinical Oncology; June 1, 2018; Chicago, IL. Abstract 8007. abstracts.asco.org/214/AbstView_214_211179.html.