Hal Barron, MD
The investigational antibody-drug conjugate GSK2857916 continued to improve progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma, according to results of a final analysis of the DREAMM-1 (BMA117159) study.1,2
Additionally, the updated data, which are from more than 1 year of follow-up and included all patients whose data were reported in the interim analysis, showed that the ADC elicited an overall response rate (ORR) of 60% and there were 3 complete responses (CRs) and 2 stringent CRs. The median PFS was 12 months (95% CI, 3.1–not estimable [NE]), and the median duration of response was 14.3 months (95% CI, 10.6—NE).
Among heavily pretreated patients who were refractory to both an immunomodulatory agent and a proteasome inhibitor (n = 32), the median PFS was 7.9 months (95% CI, 2.3¬–NE) and the ORR was 56.3%. In patients who did not receive prior treatment with daratumumab (Darzalex; n = 21), the ORR was 71.4% and the median PFS was 15.7 months (95% CI, 2.3–NE). Patients who were double refractory and were previously treated with daratumumab (n = 13) had a median PFS of 6.2 months (95% CI, 0.7-7.9) and an ORR of 38.5%. In those patients who did previously receive daratumumab, the median PFS was 6.8 months (95% CI, 1.3–NE).
Regarding safety, there were no new safety signals that were identified during the treatment period. The most commonly reported adverse events (AEs) were thrombocytopenia (63%), blurred vision (51%), and cough (40%), which were mostly grade 1/2. The most commonly reported grade 3/4 AEs were thrombocytopenia (35%) and anemia (17%) and were found to be manageable, announced GlaxoSmithKline (GSK), the manufacturer of the ADC.
“These data are very encouraging and I am excited by what they could mean for people living with multiple myeloma,” said Hal Barron, MD, chief scientific officer and president, Research and Development, GSK, in a press release. “We are aggressively advancing this potential new medicine and plan to have pivotal data to support its filing by the end of this year.”
The FDA granted GSK2857916 breakthrough therapy in November 2017 for the treatment of patients with relapsed/refractory multiple myeloma who have failed ≥3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent. The agent also received PRIME designation from the European Medicines Agency.
In the open-label, first-in-human, DREAMM-1 study, investigators evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical activity of GSK2857916 in patients with relapsed/refractory multiple myeloma and other advanced BCMA-expressing hematologic malignancies.
BCMA expression was not required for eligibility, patients had an ECOG performance status of 0 or 1, and albuminuria ≤500 mg per 24 hours. Premedication for infusion reactions was not permitted with the first dose and was not mandated at subsequent doses.
The study consisted of 2 parts: a dose-escalation phase, in which patients received GSK2857916 at escalating doses, and a dose-expansion phase in which all patients received GSK2857916 at the recommended phase II dose. The primary endpoint was safety; secondary endpoints included response rate, pharmacokinetics, and immunogenicity.
Results from part 1 of the trial, which were presented at the 2016 ASH Annual Meeting, showed that there were no dose-limiting toxicities in the 38 enrolled patients, and the phase II dose was determined as 3.4 mg/kg administered as a 1-hour infusion once every 3 weeks for up to 16 cycles.3
In part 2 of the study, 35 patients were enrolled independent of their BCMA expression levels, and there were 2 cohorts. In December 2017, cohort 1 comprised patients with relapsed/refractory multiple myeloma and the second cohort included those with BCMA-positive relapsed diffuse large B-cell lymphoma or follicular lymphoma.
Interim data on cohort 1 of the part 2 expansion phase were presented at the 2017 ASH Annual Meeting. The median patient age was 60 (range, 46-75) and 57% of patients had received ≥5 prior lines of therapy. A total 30% of patients were considered to have high-risk disease.
All patients had received an immunomodulatory agent and a proteasome inhibitor, and 89% of patients were double refractory to both agents. Forty percent of patients previously received daratumumab (Darzalex), and all but one patient was refractory to the monoclonal antibody. Thirty-four percent of patients were double-refractory to an immunomodulatory agent, a proteasome inhibitor, and had received daratumumab.
The median follow-up was 6.6 months (range, 1-10) and the median number of infusions administered was 5 (range, 1-13). The median duration of response for responding patients has not yet been reached (95% CI, 6.7–NE).