Benzinga | May 4, 2021 09:06AM EDT

ImmunityBio Reports 78% Complete Response Following Chemo-Free Combo Of IL-15 Superagonist Anktiva, Rituxan In Relapsed Non-Hodgkin Lymphoma Patients

* Durable complete response achieved in 7 of 9 (78%) CD20 sensitive patients who failed Rituxan(r) therapy in Phase 1 liquid tumor trial

* Of those patients who responded to the combination therapy of Anktiva(tm) plus Rituxan, 7 out of 7 (100%) achieved a complete response

* Chemotherapy-free regimen with minimal toxicity potentially enhances Rituxan mAb therapy with potential for broad application across liquid tumor indications

* Prolonged duration of disease without progression ranging from 18 to 24 months

CULVER CITY, Calif.--(BUSINESS WIRE)-- ImmunityBio, Inc. (NASDAQ:IBRX), a clinical-stage immunotherapy company, today announced the launch of the preclinical development of its liquid tumor pipeline with the publication of results from its Phase 1 study evaluating Anktiva(tm) (N-803), its IL-15 superagonist, in combination with Rituxan(r) (rituximab), an anti-CD20 monoclonal antibody therapy, in patients with indolent non-Hodgkin lymphoma (iNHL), who had relapsed or were refractory after two lines of therapy.

The peer-reviewed article titled "Phase 1 trial of N-803, an IL-15 receptor agonist, with rituximab in patients with indolent non-Hodgkin lymphoma" (see link HERE) published in the American Association for Cancer Research journal Clinical Cancer Research, highlights safety, efficacy, and translational data from the Company's ongoing open-label, multi-center, dose-escalation Phase 1 study (NCT02384954).

The study was designed to evaluate Anktiva in combination with rituximab in patients with iNHL, to explore the potential of Anktiva to enhance tumor-targeting of anti-CD20 therapeutic antibodies, and to determine the safety and efficacy of subcutaneous (SQ) versus intravenous (IV) administration. Anktiva has been engineered to exhibit a longer half-life and more potent trans-presentation relative to endogenous IL-15 to promote natural killer (NK) cell and T cell expansion to control cancer.

Key study results include:

* The combination regimen of Anktiva and Rituxan was well tolerated with a single reported grade 4 adverse event (AEs) and no reported grade 5 AEs

* For patients with anti-CD20 mAb sensitive disease, the overall response rate (ORR) in the SQ cohort was 78% (7 of 9)

* 7 of 7 (100%) responses in the SQ cohorts were complete remissions (CR)

* Prolonged stable disease (SD) and conversion of SD and/or partial response (PR) to CRs with a prolonged duration without progression were observed, with 8 of 12 patients without progression at 18-24 months

* For the 5 patients with anti-CD20 mAb refractory disease in both IV and SQ cohorts, the ORR was 2 of 5 (40%) with 1 CR, 1 PR, 1 SD, and 2 progressive disease (PD) with the PR and SD are ongoing at over 18 months

* In correlative immunology experiments, Anktiva in combination with Rituxan induced the expansion, activation and modulation of NK cells and CD8+ T cells, with minimal impact on CD4+ T cells and Tregs

* Multi-dimensional mass cytometry studies demonstrated remodeling of iNHL patient immune landscapes by promotion of an activation signature in nearly all main immune cell lineages including NK cells, CD8+ TEM, gd T cells, and CD14 and CD16 monocytes

Todd Fehniger, M.D., Ph.D., Washington University School of Medicine in St Louis, said, "These encouraging data suggest that Anktiva, ImmunityBio's IL-15 superagonist, has the potential to enhance the activity of an anti-CD20 therapeutic antibody. We believe the excellent safety profile seen in the SQ cohort, when combined with compelling efficacy which includes prolonged progression free survival and a 78% complete response rate in rituximab-sensitive patients, warrants the further exploration of this regimen in iNHL patients. The translational immunology data generated also provide important proof-of-mechanism, with activation of important cell population including NK Cells and CD8+ T cells, which are key in driving immunotherapy responses. Together, these results suggest Anktiva may have broad potential to enhance the activity of therapeutic monoclonal antibodies across a wide range of tumor types."

The study enrolled patients with iNHL (follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma) that were relapsed or refractory after >2 prior lines of therapy. Patients were considered anti-CD20 mAb refractory if they progressed on anti-CD20 mAb therapy within 6 months of their last dose of anti-CD20 mAb. Treatment consisted of IV rituximab 375 mg/m2 and IV or SQ N-803 (in increasing dosing cohorts of 1, 3, 6, 10, 15, 20 ?g/kg).