BCMA Antibody Drug Conjugate Active in Patients With Heavily Pretreated Myeloma

In a phase I study presented at the 2017 ASH Annual Meeting, 60 percent of patients with heavily-pretreated multiple myeloma (MM) responded to treatment with the humanized immunoglobulin G1 anti-B-cell maturation agent (BCMA) antibody conjugate GSK2857916. Suzanne Trudel, MD, of the University of Toronto, in Ontario, and colleagues presented findings of the first-in-human, open-label BMA117159 trial.

The trial consisted of dose-escalation and -expansion phases. In the dose-escalation phase, 38 patients received GSK2857916, and the maximum tolerated dose (primary endpoint) was not reached, so researchers selected 3.4 mg/kg as the recommended phase II dose. The dose-expansion phase included 35 patients (median age = 60 years; range = 46-75 years) who had received prior treatment with alkylators, proteasome inhibitors (PIs), immunomodulators (IMiDs), and hematopoietic cell transplantation, if eligible.

BCMA expression was not required for eligibility, but patients were required to have documented disease progression within 60 days of their last therapy.

More than half of participants (57%) received five or more prior lines of therapy (range = 1->10 therapies). All patients received prior PI therapy, and 97 percent were refractory. Ninety-one percent of patients were refractory to IMiDs: 40 percent received prior daratumumab, and 37 percent were refractory. Most patients (89%; n=31) were double-refractory to both PIs and IMiDs.

Patients received GSK2857916 3.4 mg/kg administered every three weeks as a one-hour intravenous infusion. They received treatment until disease progression, unacceptable toxicity, withdrawal of consent, or completion of 16 treatment cycles. The median number of treatment infusions was five (range = 1-13 infusions), and more than half (54%) received five or more infusions.

In the dose-expansion phase, 21 patients responded to treatment, for an overall response rate (ORR) of 60 percent. Responses included:

  • 1 stringent complete response (CR)
  • 2 CRs
  • 15 very good partial responses (PRs)
  • 3 PRs

Among those previously treated with daratumumab (n=14), the ORR was 43 percent (n=6; 95% CI 17.7-71.1). Eighteen of those who were double-refractory to an IMiD and PI responded to treatment (ORR=58%), and five of the 12 patients who were double-refractory and had received prior daratumumab responded (ORR=42%).

“Responses occurred early – usually within one or two doses [of GSK2857916] – and, in most cases, were durable,” Dr. Trudel said during her presentation. “Dose reductions did not lead to loss of response.”

The median duration of response was not reached, and the median progression-free survival was 7.9 months (range not reported; 95% CI 3.1 to not reached).

All patients experienced at least one adverse event (AE), the most common (occurring in ≥25% of patients) of which were corneal events (63%), thrombocytopenia (57%), anemia (29%), increased aspartate aminotransferase (29%), and cough (26%).

Corneal events occurred despite patients receiving steroid eye drops for four days with each infusion. The most common events (occurring in ≥20% of patients) were blurred vision, dry eye, and photophobia, most of which were grade 1/2 and reversible.

The most common grade 3/4 AEs (reported by ≥10% of patients) were thrombocytopenia (34%) and anemia (14%). Fourteen patients (40%) reported serious AEs.

Eight patients experienced infusion-related reactions that occurred during first infusion. These resolved and did not recur with subsequent infusions. Eighteen patients discontinued GSK2857916 because of disease progression (n=15), AEs (n=2), or patient decision (n=1), while 17 patients continue to receive the drug.

“The target and therapeutic mechanisms of action differentiate GSK2857916 from [other] MM [drugs],” the authors noted. “GSK2857916 demonstrated … deep and durable responses in heavily pretreated … [patients with] MM who have limited treatment options.”

The study is limited by its small patient population and lack of a comparator arm.

The researchers have also begun enrolling patients into a lymphoma cohort to assess GSK2857916.

GlaxoSmithKline, Seattle Genetics, and BioWa supported the study.

The authors report financial relationships with Astellas, Janssen, Takeda, GlaxoSmithKline, Celgene, and Amgen.


Trudel S, Lendvai N, Popat R, et al. Deep and durable responses in patients (pts) with relapsed/refractory multiple myeloma (MM) treated with monotherapy GSK2857916, an antibody drug conjugate against B-cell maturation antigen (BCMA): preliminary results from part 2 of study BMA117159. Abstract #741. Presented at the 2017 American Society of Hematology Annual Meeting, December 11, 2017; Atlanta, GA.