The agent, given at a 400 µg daily dose, reduced tumor burden in 70% of patients, and eliminated even small traces of cancer cells in the bone marrow and blood — a status called minimal residual disease negative — in 40% of patients.
The study, “Treatment with AMG 420, an anti-B-Cell Maturation Antigen (BCMA) Bispecific T-cell Engager (BiTE®) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study,” was recently presented at the American Society of Hematology (ASH) 2018 Meeting in San Diego.
AMG 420 is a type of immunotherapy that brings cancer cells closer to immune cells. The agent is made using Amgen’s proprietary BiTE or “bispecific T-cell engager” technology and consists of two antibodies fused together that target the BCMA protein in myeloma cells and the CD3 protein at the surface of T-cells.
The Phase 1 trial (NCT02514239), conducted in France and Germany, was designed to determine the maximum tolerated dose and dose-limiting toxicities of AMG 420 in relapsed or refractory multiple myeloma patients.
Preliminary measures of efficacy — including objective response rate, duration of response, time to disease progression or death, and minimal residual disease response rate — were also assessed as secondary endpoints.
The study included 42 patients who had been treated with at least two prior lines of therapy, including a proteasome inhibitor — such as Velcade (bortezomib), Kyprolis (carfilzomib), or Ninlaro (ixazomib) — and an immunomodulatory imide drug — such as Revlimid (lenalidomide) or Pomalyst (pomalidomide).
Patients received escalating doses of AMG 420 — between 0.2 and 800 µg daily — given as a continuous infusion in the first four weeks of every six-week cycle.
Overall, 13 patients responded to the treatment, including seven with complete responses. But responses were particularly better in the patients who received a 400 µg daily dose, with seven of 10 patients responding to treatment, and four achieving minimal residual disease negativity. Also, six patients were still responding to treatment 7.5 months after entering the trial.
“In this first-in-human study, AMG 420, a short half-life BiTE targeting BCMA, showed encouraging evidence of activity in patients with relapsed and/or refractory multiple myeloma,” researchers said. “No major toxicities were observed up to 400 µg/d, which is the recommended dose for further investigation.”
One dose-limiting toxicity was reported in the group of patients treated with the 400 µg dose. The treatment caused impairment of peripheral nerve cells, which was resolved after immunoglobulin and corticosteroid therapy.
A total of 20 patients experienced serious adverse events during the trial, with 17 requiring hospitalization. These included infections, peripheral nerve damage, liver failure, cardiac failure, fluid accumulation, biliary obstruction, spinal cord compression, renal failure, and weight loss. Cytokine release syndrome (CRS), a potentially life-threatening event caused by an overactive immune system, was reported in 16 patients.
Two patients died from adverse events, but they were not considered related to AMG 420 treatment.
“Building on our success with the only approved BiTE immunotherapy available for patients, Amgen is emphasizing our commitment to the potential of this platform by advancing the development of approximately a dozen novel molecules across hematologic and solid tumor targets in hopes of continuing to offer meaningful advances to patients in need,” David M. Reese, MD, executive vice president of research and development at Amgen, said in a press release.
The U.S. Food and Drug Administration recognized the potential of AMG 420 by granting it Fast Track status, which is expected to support and facilitate its clinical development and expedite its regulatory review.