A subcutaneous formulation of Johnson & Johnson’s BCMAxCD3 bispecific antibody teclistamab has achieved a 73% total response charge in a small trial of closely pretreated a number of myeloma sufferers.
J&J offered knowledge on an intravenous model of the drug in May, 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 part 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 part 2 dose responded. 5 contributors 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 important toxicity. Whereas 64% of sufferers on the part 2 subcutaneous dose skilled cytokine launch syndrome, all these occasions have been grade 1 or 2 and none prompted a affected person to discontinue. There was one grade 1, reversible neurotoxicity occasion. The combo of efficacy and tolerability seen to this point has persuaded J&J to up its wager on teclistamab.
“It’s still early … but certainly the profile of teclistamab looks very, very promising to us and one that is worthy of aggressive investment and development. That’s the approach that we’re taking now,” stated Craig Tendler, vice chairman, oncology scientific improvement and world medical affairs at J&J.
An evaluation of 11 sufferers who had full responses to both the intravenous or subcutaneous formulations confirmed eight contributors have been minimal residual disease-negative at a threshold of 10-6.
The responses, which J&J stated deepened over time, have been seen in sufferers failed by a number of different therapies. Throughout the examine, sufferers had acquired a median of six prior strains of therapy. Virtually 40% of the contributors have been refractory to 2 or extra immunomodulatory brokers, two or extra proteasome inhibitors and an anti-CD38 remedy. Such sufferers have few therapy choices as we speak.
“To be able to have a well-tolerated antibody be given that can get them into a very fast remission — time to first response is also quite quick — is certainly an important milestone for these patients in terms of getting their disease under control,” Tendler stated.
J&J is one in all a substantial variety of drug builders focusing on BCMA to provide 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 nevertheless 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 determine it as a upkeep remedy and within the smoldering myeloma area. The swap from intravenous to subcutaneous formulations may gain advantage J&J’s push into different components of the therapy pathway, together with by enabling it to maneuver away from weekly dosing.
“We have cohorts that will be looking at bi-weekly and then ultimately monthly dosing. That is definitely in the plan for further optimization of dosing, especially in settings like maintenance therapy. We want to have the most flexible dosing schedule so that this is not inconvenient for patients,” Tendler stated.
With different corporations posting encouraging knowledge and subcutaneous formulations, J&J will face competitors because it seeks to determine teclistamab however approaches the problem on the again of its success reshaping a number of myeloma therapy with Darzalex.