Armed with two positive phase 3 trial readouts and the hope that at least one will show a significant patient survival benefit, GSK thinks it has the data to convince doctors and the FDA that the once-failed antibody-drug conjugate (ADC) Blenrep can work in multiple myeloma.
In a second phase 3 win, Blenrep cut the risk of cancer progression or death by 48% compared with Takeda’s Velcade (V) in their respective combinations with Bristol Myers Squibb’s Pomalyst (P) and the steroid dexamethasone (d). The results came from the DREAMM-8 trial conducted in multiple myeloma patients who had tried at least one prior line of therapy and were shared at the American Society of Clinical Oncology 2024 annual meeting.
After a median follow-up of 21.8 months, the median progression-free survival (PFS) was still not reached for the Blenrep arm, versus 12.7 months for control.
The latest data set follows a recent readout from the DREAMM-7 trial, in which Blenrep beat Johnson & Johnson’s Darzalex (D) by 59% on PFS in their respective pairings with Vd. That study also tested the regimens in the second line or later.
With the two positive trials, GSK plans to file Blenrep with the FDA in the second half of this year, Hesham Abdullah, M.D., GSK’s head of oncology R&D, told Fierce Pharma. The company hopes to reintroduce Blenrep in the U.S. following a market withdrawal in the late-line setting, which was triggered by the drug’s phase 3 flop as a monotherapy.
During an ASCO press briefing on Saturday, Suzanne Trudel, M.D., from Princess Margaret Cancer Centre in Canada, who presented the DREAMM-8 results, and Oreofe Odejide, M.D., an ASCO-invited expert from Dana-Farber Cancer Institute, said the data support Blenrep’s return as a treatment option for relapsed myeloma.
If approved, Blenrep, a BCMA-directed ADC, will compete with J&J and Legend Biotech’s powerful BCMA CAR-T therapy, Carvykti, in second-line treatment, plus BMS' rival CAR-T, Abecma, in later lines.
By a cross-trial comparison, the 48% PFS benefit seen in Blenrep’s latest DREAMM-8 study looks smaller than the 59% result recorded by Carvykti in its CARTITUDE-4 trial. The Carvykti study used PVd or DPd in the control group.
Abdullah said GSK is optimistic that the earlier DREAMM-7 study will be able to meet statistical significance on overall survival. At a prior interim analysis, Blenrep-Vd preliminarily pared down the risk of death by 43% versus PVd. At the time, the showing just narrowly missed statistical significance.
By comparison, J&J’s Carvykti was also linked to a preliminary 43% reduction in the risk of death versus PVd or DPd during a recent data cut, although that number remained immature. Bristol Myers’ Abecma, in a third-line setting, didn’t show any patient survival benefit in the phase 3 KarMMa-3 study without adjusting for patient crossovers. Given the progress of that study, the FDA figured it’s unlikely that the BMS trial will eventually hit statistical significance on overall survival.
As for the current DREAMM-8 trial, Blenrep showed a favorable trend toward a 23% reduction in the risk of death at the interim analysis. GSK expects the size of benefit will widen over time, Abdullah said, without expressing the same level of confidence on reaching statistical significance.
Abdullah also flagged some important differences between the trials. In DREAMM-7, about half of the trial participants had tried BMS’ Revlimid, including 30% who were refractory to the immunomodulating agent. In DREAMM-8, all patients had previously tried Revlimid, including 80% who were refractory.
Besides the trials' efficacy results, there’s the CAR-T therapies’ known drawbacks around lengthy manufacturing timelines and complicated administration procedures. The drugs are required to be given at designated treatment centers.
Both CAR-T trials recorded an early risk of death for patients in the cell therapy groups. As the early death cases were mostly seen in patients who didn’t live long enough to receive their assigned CAR-T therapies, the FDA has argued that these individualized medicines’ production timelines were to blame.
Conversely, Blenrep didn’t have that early death signal. As an off-the-shelf therapy, it could be more accessible to patients in the community setting, where more than 70% of myeloma patients are currently treated, Abdullah noted.
“Access, consistency of treatment effects and that effect across multiple patient subgroups, and overall survival” will be the key differentiators for Blenrep, the GSK exec said.
Based on the positive results in previously treated patients, both J&J/Legend and BMS have kicked off phase 3 trials for their CAR-Ts in the first-line setting. GSK is taking a pause to dig into Blenrep’s existing data and mull over its earlier-line strategy, Abdullah said.