On May 4, 2021 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported the launch of the preclinical development of its liquid tumor pipeline with the publication of results from its Phase 1 study evaluating AnktivaÔ (N-803), its IL-15 superagonist, in combination with RituxanÒ (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 (Press release, ImmunityBio, MAY 4, 2021, https://immunitybio.com/immunitybio-announces-78-percent-complete-response-following-chemotherapy-free-combination-of-il-15-superagonist-anktiva-with-rituxan-in-relapsed-non-hodgkin-lymphoma-patients/ [SID1234579039]).
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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 (AACR) (Free AACR Whitepaper) 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 µg/kg).