Pomalidomide

Johnson & Johnson reported another positive Phase III study in relapsed or refractory multiple myeloma, saying its dual bispecific combination comprising Tecvayli (teclistamab) and Talvey (talquetamab) significantly extended both progression-free survival (PFS) and overall survival (OS) in patients who had received one to four prior lines of therapy."These findings further reinforce immunotherapy as a cornerstone of multiple myeloma care," said Yusri Elsayed, global therapeutic area head for oncology, in a company release Thursday.Tecvayli, a bispecific that targets BCMA, is currently indicated for multiple myeloma in the fifth-line setting; earlier this year it also obtained an approval for use together with J&J's Darzelex Faspro (daratumumab/hyaluronidase) in patients who have received at least one prior line of therapy.Talvey, which zeroes in on GPRC5D, is also currently approved for fifth-line multiple myeloma. J&J has been looking to move the therapy earlier in the course of treatment and recently posted Phase III results from the MonumenTAL-3 study, where Talvey plus Darzalex Faspro lowered the risk of disease progression or death by up to 72% at a median follow-up of two years.PFS rate of 89%Thursday's topline readout centred on MonumenTAL-6, a three-arm trial evaluating Talvey plus Tecvayli, Talevy plus pomalidomide, or investigator's choice standard care in an estimated 795 patients who received one to four prior lines of therapy, including an anti-CD38 antibody and lenalidomide.On the primary endpoint, J&J's BCMA- and GPRC5D-targeting combo reduced the risk of disease progression or death by 89% versus investigator's choice. It also lowered the risk of death, a secondary goal of the study, by 62%. Both outcomes were statistically significant."This represents the lowest hazard ratio seen across any Phase III study evaluating bispecific therapies in relapsed/refractory multiple myeloma," the company said.The other experimental arm of the study, Talevy and pomalidomide, also succeeded on both those measures; J&J said this arm achieved a PFS rate of 73%. Full results will be presented at a future major medical meeting and shared with global health authorities.The overall safety profiles for the two treatment arms were also consistent with the known safety profiles of each monotherapy, the company said. An independent data monitoring committee has now recommended unblinding the study at the first interim analysis.Key opinion leaders told FirstWord in a recent report that they expected MonumenTAL-3 and MonumenTAL-6 to succeed. However, one expert suggested that Talvey's "side-effect profile is a sufficient deterrent to numb the enthusiasm for the drug," while another said combination regimens may allow lower Talvey dosing that could improve tolerability (see – KOL Insight - Multiple Myeloma).

Johnson & Johnson has unveiled massive phase 3 survival data for its dual bispecific combination in earlier-line multiple myeloma, delivering another catalyst that could add a new twist in the commercial trajectories of off-the-shelf T-cell engagers versus personalized CAR-T therapies. The combination of J&J’s Tecvayli and Talvey slashed the risk of disease progression or death by 89% compared to standard-of-care cocktails in second- to fifth-line multiple myeloma patients, according to results from the phase 3 MonumenTAL-6 trial. In another remarkable showing, the two T-cell engagers targeting BCMA and GPRC5D delivered a 62% reduction in the risk of death, J&J announced Thursday. By the numbers, MonumenTAL-6 lived up to its name. Efficacy of this magnitude in progression-free survival (PFS) and overall survival (OS) benefits is exceptionally rare in phase 3 oncology trials, and MonumenTAL-6 hit those goals at its first interim analysis. For context, a 60% OS improvement in pancreatic cancer recently earned Revolution Medicines’ daraxonrasib a standing ovation at the 2026 American Society of Clinical Oncology annual meeting. The MonumenTAL-6 results naturally invite comparison to the phase 3 Cartitude-4 trial, in which J&J and Legend Biotech’s CAR-T therapy, Carvykti, demonstrated a 59% PFS improvement over traditional standard treatment in second- or later-line multiple myeloma. The BCMA-directed cell therapy later delivered a statistically significant 45% OS benefit , at which point its PFS benefit expanded to 71%. J&J’s new readout comes a few months after the FDA approved Tecvayli in combination with the company’s anti-CD38 antibody, Darzalex, for relapsed or refractory multiple myeloma under the Commissioner’s National Priority Voucher pilot program. While the phase 3 MajesTEC-3 study supporting that clearance mainly enrolled patients who had not received a CD38 antibody in the first-line setting, MonumenTAL-6 is being conducted in a CD38-exposed population, including roughly 80% who were refractory to Darzalex. If approved, the Tecvayli-Talvey doublet will inevitably encroach further on Carvykti’s second-line market. However, even with numerically higher efficacy numbers by cross-trial comparison, the bispecific combo is not expected to displace CAR-T or even command a dominant share. “Multiple myeloma patients are in a very good place right now because all these regimens in the relapse setting have now a survival advantage,” Yusri Elsayed, M.D., Ph.D., J&J’s oncology global therapeutic area head, said in an interview with Fierce Pharma. Despite the trial’s impressive efficacy data, Elsayed noted that combining two bispecific agents means the Tecvayli-Talvey regimen will likely be reserved for a select subset of patients, potentially those at high risk of progression who receive care at large academic centers. For one thing, Talvey, a GPRC5DxCD3 T-cell engager, has proven useful following progression on a BCMA therapy. Deploying both mechanisms upfront could deprive doctors of a vital salvage option down the line. While Carvykti has been hailed as a potential cure for myeloma patients, about half of pretreated high-risk patients—and 30% of standard-risk risk patients—are still expected to progress within three years of treatment, according to results from Cartitude-4. Elsayed agreed that GPRC5D agents like Talvey—whether used alone or in combination—will mostly be used in later lines , suggesting that it remains “the easiest way” for physicians to sequence therapies. In earlier-line settings, J&J expects that “people are going to use BCMA-directed therapy—either do Dara and Tec, or Carvykti,” Elsayed said. “There is going to be very, very small percentage of patients who might want to use the Tec and Tal combination for a specific reason.” For a more direct cross-trial comparison, within the Darzalex-pretreated subgroup of Cartitude-4, Carvykti’s PFS advantage mounted to 77% in the primary analysis and 76% in the longer follow-up; at the latter time point, the cell therapy’s OS benefit stood at 39%. Other differences complicate direct head-to-head comparisons between Cartitude-4 and MonumenTAL-6. For example, the Carvykti trial required patients to be refractory to lenalidomide (Revlimid), whereas the bispecific study requires only prior exposure. Because Cartitude-4 enrolled both Darzalex-naïve and pretreated patients, the control-arm regimens differed, as well. Information such as subsequent treatments will also be important context to understand the OS results in MonumenTAL-6. In terms of safety, Elsayed said he was a bit surprised by Tecvayli and Talvey’s tolerability profile. The doublet showed fewer infections than historically observed with Tecvayli monotherapy and also fewer GPRC5D-related side effects than seen with Talvey alone. Elsayed attributed this in part to physicians becoming more adept at managing those adverse events over years of practice, as well as the lower dosing intensity for each component in the combo than when they’re used alone. MonumenTAL-6 also includes a third arm evaluating Talvey paired with pomalidomide (Pomalyst). That regimen also generated a statistically significant 73% PFS advantage over the control arm. While its OS trend currently sits at a favorable 45% improvement, it has not reached statistical significance at this interim analysis, Elsayed told Fierce. “We are very confident that with more patients and with time toward the end of this year or beginning of next year, it will also be statistically significant,” the J&J exec said.