GSK Compound Showing Durable Response Rates in Advanced Multiple Myeloma, New Phase 1 Trial Data Find

New data from a Phase 1 clinical trial show treatment with GlaxoSmithKline‘s investigational antibody-drug conjugate, GSK2857916, was linked to year free of disease progression in patients with relapsed or refractory multiple myeloma.

The results — covering 14 additional months of follow-up — again show 60% of these advanced patients responding to treatment (overall response rate or ORR), confirming the findings of an earlier, interim analysis presented at the American Society of Haematology Congress in 2017.

In addition, 15% of patients showed complete response, or no signs of cancer, an improvement on interim findings. Median progression-free survival was 12 months (up from 7.9 months), and median duration of response (previously not estimated) was 14.3 months.

“These data are very encouraging and I am excited by what they could mean for people living with multiple myeloma,” Hal Barron, chief scientific officer and president, R&D at GlaxoSmithKline, said 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 research, “Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study,” was published in the Blood Cancer Journal

The open-label, two-part, and multi-center DREAMM-1 study (NCT02064387) is evaluating the safety, pharmacological profile, clinical activity and immunogenicity – whether it triggers an immune response – of GSK2857916 in people with relapsed or refractory multiple myeloma and other advanced blood cancers expressing B-cell maturation antigen (BCMA). Fourteen of the 35 enrolled adults previously tried more than five lines of therapy.

A cell signaling pathway involving BCMA has been implicated in myeloma cell growth and survival. BCMA is detected at the cell membrane of all myeloma cell lines.

GSK2857916 is an antibody-drug conjugate comprising an anti-BCMA monoclonal antibody bound to auristatin F, a molecule that induces cell death.

After the trial’s first part into escalating doses of the treatment candidate, all 35 patients were given GSK2857916 at 3.4 mg/kg — the recommended dose identified for part two — every three weeks.

Among heavily pre-treated patients not previously taking Darzalex (daratumumab, by Janssen), the response rate was 71% and the median time without multiple myeloma progression was 15.7 months. Pre-treatment with Darzalex was associated with a response rate of 38.5% and 6.8 months without disease worsening.

Among patients who did not respond to both immunomodulators like Revlimid (lenalidomide, by Celgene), and to proteasome inhibitors like Velcade (bortezomib, by Takeda) — 56.3% responded to GSK2857916, with a median progression-free survival of 7.9 months.

In turn, patients previously treated with Darzalex but refractory (unresponsive) to immunomodulators and proteasome inhibitors had 6.2 months without cancer progression.

No new safety signals were identified in part two. The most frequent side effects were lower platelet counts, blurred vision, and cough, all three mostly mild or moderate. The most common serious or life-threatening adverse events were low platelet counts and anemia, both manageable.

“Overall, our results suggest that GSK2857916 is a promising therapy for patients with relapsed and refractory [multiple myeloma], including those in whom all other standard and available therapies have failed,” the researchers wrote.

Paul Giusti, president and CEO at the Multiple Myeloma Research Foundation, added that experts with this group “are encouraged by the results from this early study, and we look forward to seeing additional data later this year.”

GSK2857916 uses technology licensed from Seattle Genetics and BioWa. The treatment candidate was designated a breakthrough therapy by the U.S. Food and Drug Administration and given a PRIME designation by the European Medicines Agency in 2017. Both awards are intended to quicken and support the development of promising therapies.