Both doses of GlaxoSmithKline’s BCMA-targeting antibody-drug conjugate (ADC) shrank tumors in about one-third of patients with advanced multiple myeloma in a phase 2 study. The numbers are in line with response rates typically seen in studies involving very sick patients, but the candidate could do even better in earlier lines of treatment.
The study, published Monday in The Lancet Oncology, tested each dose of belantamab mafodotin—2.5 mg/kg and 3.4 mg/kg—in about 100 patients who had tried a median of seven other treatments. These included a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody such as Johnson & Johnson’s Darzalex.
Of the 97 patients who received the lower dose, 30 patients, or 31%, had their tumors shrink, and three patients saw them banished entirely. The response rate was similar in the 99 patients who received the higher dose: 34%.
The lower dose of the ADC kept cancer at bay for a median 2.9 months, while the higher dose staved off cancer progression for a median 4.9 months. With six months of follow-up, there are not yet enough data to determine how long the drug helped keep patients alive.
Although both doses logged similar response rates, the study investigators recommended the lower dose for future work thanks to its better safety profile. Patients who received that dose had a lower rate of side effects such as low levels of platelets and white blood cells, bleeding and infections. Three patients in the lower-dose group and seven patients on the higher dose died from side effects, with one death in each group deemed potentially linked to the treatment.
It’s important to note that the phase 2 study tested belantamab mafodotin in much sicker patients than an earlier study, which posted a 60% response rate, Axel Hoos, GlaxoSmithKline’s global senior vice president of oncology R&D, told FierceBiotech.
“That 60% response rate was in an earlier line of treatment. The [phase 1] DREAMM-1 study started before Darzalex was approved and the vast majority of patients did not have Darzalex before and were not refractory to Darzalex. It was a much healthier patient population,” Hoos said.
GSK is seeking approval for belantamab mafodotin as a fourth-line treatment for relapsed or refractory multiple myeloma, but it is testing the medicine in earlier lines of treatment. It's running trials for the prospect both as a single agent and in combination with other drugs, both experimental and approved, such as Merck's PD-1 blockbuster Keytruda.
"Starting in fourth line means about 10,000 patients per year, globally,” Hoos said. “If we go to first line, it can go to as high as 65,000 patients per year, globally. The big increase comes with access to combination.”
It’s no secret that multiple myeloma is a field crowded with BCMA-targeting treatments. So, what sets GSK’s prospect apart from the CAR-T therapies and bispecific antibodies out there? At the heart of the matter is the antibody, attached to a cell-killing agent using technology from Seattle Genetics.
“We are the first BCMA-targeting agent making a submission for registration and we’ve been able to do that because it is an antibody,” Hoos said. “At the end of the day, it took us three months to enroll a registrational trial with an antibody … because we can manufacture it easily, we can scale it up and we can make it available to patients fairly straightforwardly.”
The treatment is given in 30-minute infusions every three weeks, compared to bispecifics, which have a much longer infusion period, Hoos said. It also has a leg up on CAR-T treatments, which can take a long time to make and so are difficult to make available to large numbers of patients.
“Now we’ve shown it to have a robust response rate in the last line of therapy that is durable and likely combinable with other standard-of-care treatments. When you go into earlier lines, that is very important because if you can’t combine in this crowded space, it is very hard to go earlier line,” Hoos said.
But whatever you do, Hoos said, don’t call it a comeback for the British drugmaker, which traded away its marketed oncology meds to Novartis back in 2015.
That deal "created the public perception that GSK had left oncology. That was never true,” he said. “We have built a pipeline over the last six to seven years purely based on innovation that did not go to Novartis. This BCMA-targeting agent, belantamab mafodotin, is the first from this new portfolio … and there are many other compounds following.
“People are saying GSK is back in oncology," he added. "Actually, we never left.”