The investigational bispecific T-cell engager (BiTE) from Amgen — currently named AMG 420 — continued to show quick, high response rates in patients with relapsed/refractory multiple myeloma, according to the latest data from the first-in-human phase 1 dose-escalation study presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (ClinicalTrials.gov identifier: NCT02514239).1
AMG 420 targets B-cell maturation antigen (BCMA) on the surface of tumor cells and in theory, works by first binding BCMA and then CD3 on the surface of T cells, not only drawing the T cell near to kill the tumor cell, but also triggering T-cell proliferation. And while AMG 420 is the first BiTE to show high clinical activity in multiple myeloma, it’s far from the only BCMA-targeted therapy in development to do so.
The “Perfect Target”
During an interview with Cancer Therapy Advisor, Nikhil Munshi, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, said that for myeloma, BCMA is the “perfect target.” Although he was not involved in the study, Dr Munshi explained that almost all patients with myeloma express BCMA, and while healthy plasma cells also express BCMA, the toxicity is limited.
Perhaps not surprisingly then, the BCMA-targeted therapies in development run the gamut of drug types — antibody-drug conjugates, chimeric antigen receptor (CAR) T (CAR-T) cells, bispecific antibodies, trispecific antibodies — and the few that have reached clinical trials have generated encouraging results.2 Specifically, belantamab mafodotin (GSK2857916), an antibody-drug conjugate from GlaxoSmithKline, has shown a response rate of 60%.3 In addition, several CAR-T cell therapies are in clinical trials, with some having shown response rates of more than 80% and another even reaching 100% in a small group of patients.4,5,6
The first clinical data for AMG 420 were unveiled at the 2018 American Society of Hematology (ASH) Annual Meeting, earning the agent a fast track designation, and the latest data presented at ASCO included 42 patients.7,8 Patients first received doses ranging from 0.2 µg/d to 800 µg/d and 13 responded, starting at dosing as low as 6.5 µg/day and all the way up to 800 µg/day. The responses included 6 complete responses (CRs), 3 stringent CRs, 2 very good partial responses (VRPRs), and 2 partial responses (PRs) — and the responses occurred quickly: The median time to response was 1 month and the majority of patients (11 of 13) responded during the first cycle.
For the 10 patients who received AMG 420 at 400 µg/d — which is now considered the recommended dose — 7 responses (5 minimal residual disease-negative CRs, 1 VGPR, and 1 PR) were seen, yielding a response rate of 70%.
“I’ve been treating myeloma only for the last 30 years, and I have not seen responses like this in such advanced patient populations,” said Dr Munshi, speaking about BCMA-targeted therapies in general. However, he said, the issue for BCMA-targeted therapies now is the duration of response, which for AMG 420 at 400 µg/d was 9 months (range, 5.8–13.6), with 2 patients still on treatment. “[BiTEs] work well, but the duration of responses that was presented can be improved,” he said.