A subcutaneous formulation of Johnson & Johnson’s BCMAxCD3 bispecific antibody teclistamab has achieved a 73% total response fee in a small trial of closely pretreated a number of myeloma sufferers.
J&J introduced knowledge on an intravenous model of the drug in Could, revealing eight of the 12 sufferers to get a sure dose responded to the remedy. Since then, J&J has moved a subcutaneous formulation of the bispecific antibody right into a pivotal section 2 scientific trial. J&J arrived on the American Society of Hematology 2020 Annual Assembly with knowledge to help its determination to advance the formulation.
Sixteen of the 22 sufferers to obtain the 1500 µg/kg subcutaneous section 2 dose responded. 5 members had full responses. All bar one of many responders was progression-free after median follow-up of three.9 months.
J&J achieved these responses with out inflicting vital toxicity. Whereas 64% of sufferers on the section 2 subcutaneous dose skilled cytokine launch syndrome, all these occasions have been grade 1 or 2 and none brought about a affected person to discontinue. There was one grade 1, reversible neurotoxicity occasion. The combo of efficacy and tolerability seen up to now has persuaded J&J to up its guess on teclistamab.
“It is nonetheless early … however definitely the profile of teclistamab seems to be very, very promising to us and one that’s worthy of aggressive funding and improvement. That is the method that we’re taking now,” mentioned Craig Tendler, vp, oncology scientific improvement and international medical affairs at J&J.
An evaluation of 11 sufferers who had full responses to both the intravenous or subcutaneous formulations confirmed eight members have been minimal residual disease-negative at a threshold of 10-6.
The responses, which J&J mentioned deepened over time, have been seen in sufferers failed by a number of different therapies. Throughout the examine, sufferers had obtained a median of six prior strains of remedy. Virtually 40% of the members have been refractory to 2 or extra immunomodulatory brokers, two or extra proteasome inhibitors and an anti-CD38 remedy. Such sufferers have few remedy choices as we speak.
“To have the ability to have a well-tolerated antibody be given that may get them into a really quick remission — time to first response can be fairly fast — is definitely an essential milestone for these sufferers by way of getting their illness underneath management,” Tendler mentioned.
J&J is one in every of a substantial variety of drug builders focusing on BCMA to present relapsed/refractory a number of myeloma sufferers new choices. Amgen, Bristol-Myers Squibb, Pfizer and Regeneron all have anti-BCMA bispecifics in improvement, GlaxoSmithKline is closing in on approval of an antibody-drug conjugate aimed on the goal and a clutch of corporations, together with J&J, are engaged on cell therapies.
Initially, J&J, like its rivals, goes after closely pretreated sufferers however it plans to maneuver into earlier strains of remedy. J&J is testing the bispecific together with its anti-CD38 blockbuster Darzalex and has aspirations to ascertain it as a upkeep remedy and within the smoldering myeloma house. The swap from intravenous to subcutaneous formulations may benefit J&J’s push into different elements of the remedy pathway, together with by enabling it to maneuver away from weekly dosing.
“We have now cohorts that shall be bi-weekly after which in the end month-to-month dosing. That’s positively within the plan for additional optimization of dosing, particularly in settings like upkeep remedy. We need to have essentially the most versatile dosing schedule in order that this isn’t inconvenient for sufferers,” Tendler mentioned.
With different corporations posting encouraging knowledge and subcutaneous formulations, J&J will face competitors because it seeks to ascertain teclistamab however approaches the problem on the again of its success reshaping a number of myeloma remedy with Darzalex.