A subcutaneous formulation of Johnson & Johnson’s BCMAxCD3 bispecific antibody teclistamab has achieved a 73% overall response rate in a small trial of heavily pretreated multiple myeloma patients.
J&J presented data on an intravenous version of the drug in May, revealing eight of the 12 patients to get a certain dose responded to the therapy. Since then, J&J has moved a subcutaneous formulation of the bispecific antibody into a pivotal phase 2 clinical trial. J&J arrived at the American Society of Hematology 2020 Annual Meeting with data to support its decision to advance the formulation.
Sixteen of the 22 patients to receive the 1500 µg/kg subcutaneous phase 2 dose responded. Five participants had complete responses. All bar one of the responders was progression-free after median follow-up of 3.9 months.
J&J achieved those responses without causing significant toxicity. While 64% of patients on the phase 2 subcutaneous dose experienced cytokine release syndrome, all those events were grade 1 or 2 and none caused a patient to discontinue. There was one grade 1, reversible neurotoxicity event. The mix of efficacy and tolerability seen to date has persuaded J&J to up its bet 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,” said Craig Tendler, vice president, oncology clinical development and global medical affairs at J&J.
An analysis of 11 patients who had complete responses to either the intravenous or subcutaneous formulations showed eight participants were minimal residual disease-negative at a threshold of 10-6.
The responses, which J&J said deepened over time, were seen in patients failed by multiple other therapies. Across the study, patients had received a median of six prior lines of treatment. Almost 40% of the participants were refractory to two or more immunomodulatory agents, two or more proteasome inhibitors and an anti-CD38 therapy. Such patients have few treatment options today.
“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 said.
J&J is one of a considerable number of drug developers targeting BCMA to give relapsed/refractory multiple myeloma patients new options. Amgen, Bristol-Myers Squibb, Pfizer and Regeneron all have anti-BCMA bispecifics in development, GlaxoSmithKline won approval of an antibody-drug conjugate aimed at the target, Blenrep, this year and a clutch of companies, including J&J, are working on cell therapies.
Initially, J&J, like its rivals, is going after heavily pretreated patients but it plans to move into earlier lines of therapy. J&J is testing the bispecific in combination with its anti-CD38 blockbuster Darzalex and has aspirations to establish it as a maintenance therapy and in the smoldering myeloma space. The switch from intravenous to subcutaneous formulations could benefit J&J’s push into other parts of the treatment pathway, including by enabling it to move 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 said.
With other companies posting encouraging data and looking at subcutaneous formulations, J&J will face competition as it seeks to establish teclistamab but approaches the challenge on the back of its success reshaping multiple myeloma treatment with Darzalex.