Lenzilumab before CAR-T induces high response rates without severe toxicities
Click Here to Manage Email Alerts
A combination of lenzilumab and axicabtagene ciloleucel induced an 83% overall response rate among patients with advanced diffuse large B-cell lymphoma, according to topline data released by the agent’s manufacturer.
Results of the phase 1b portion of the ZUMA-19 trial also showed no incidence of severe cytokine release syndrome or neurotoxicity at the recommended phase 2 dose.
The multicenter ZUMA-19 study evaluated lenzilumab (Humanigen), an anti-human GM-CSF monoclonal antibody, in combination with axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead) — a CD19-directed chimeric antigen receptor T-cell therapy — among adults with relapsed or refractory DLBCL.
The study enrolled six patients who received lenzilumab at a dose of either 600 mg (n = 3) or 1,800 mg (n = 3) prior to CAR T-cell therapy.
The study met its phase 1 primary endpoint, with no dose-limiting toxicities or grade 2 or higher CRS or neurotoxicity within 28 days of axicabtagene ciloleucel infusion.
Researchers reported an ORR of 83%. Four patients achieved complete responses to therapy. One patient who received the 600 mg dose had grade 3 neurotoxicity that lasted 2 days.
All three patients who received the recommended phase 2 dose of 1,800 mg lenzilumab responded to therapy; two patients achieved complete response. No patients in this cohort had grade 2 or higher CRS or neurotoxicity, and no adverse events related to lenzilumab occurred throughout the study, according to the manufacturer.
“These encouraging results from ZUMA-19 provide further proof of concept that lenzilumab may break the linkage between efficacy and toxicity (CRS and [neurotoxicity]) widely associated with CAR-T, and may improve durability of response,” Dale Chappell, MD, MBA, chief scientific officer for Humanigen, said in a company-issued press release. “We believe these data warrant a larger study involving multiple CAR-T therapies.”
Humanigen has ended its collaboration with Kite Pharma on the ZUMA-19 study, according to the press release. The release stated that the company will submit plans to the FDA for a randomized, multicenter phase 2 study to evaluate the safety and efficacy of lenzilumab with all commercially available CD19-directed CAR T-cell therapies for DLBCL.
“Humanigen is pleased to be in a position to proactively develop lenzilumab across the CAR-T landscape and further expand its pipeline,” Cameron Durrant, MD, MBA, CEO of Humanigen, said in the release. “We thank Kite for their sponsorship and contribution that has allowed Humanigen to progress to this exciting point.”
Click Here to Manage Email Alerts