On May 20, 2021 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported an upcoming poster presentation highlighting its chemotherapy free regimen of interleukin-15 (IL-15) superagonist Anktiva (also called N-803) in combination with checkpoint therapy in patients who had relapsed from checkpoint inhibitors, at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place virtually this year from June 4 through June 8, 2021 (Press release, ImmunityBio, MAY 20, 2021, View Source [SID1234580344]).

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The Phase 2 study, titled "Preliminary data from QUILT 3.055: A Phase 2 multi-cohort study of N-803 (IL-15 superagonist) in combination with Checkpoint Inhibitors (CPI)", details data highlighting the safety and clinical benefit of adding Anktiva to checkpoint inhibitor therapy in second-line or greater treatment regimens in multiple cancer types, a basket trial.

Anktiva is designed to activate natural killer cells and CD8+ T cells, without the activation of T-reg cells that can suppress anti-tumor activity. In this Phase 2 study, Anktiva was administered to each patient in combination with a checkpoint inhibitor that had previously yielded a complete response, partial response, or six months of stable disease in that patient in the setting of first-, second- and third-line therapy before disease progression resumed.

"We are encouraged by the trend to date toward Anktiva’s safety, tolerability and clinical benefit that is robust across several types of historically difficult-to-treat cancers, which aligns with Anktiva’s mechanism of action being agnostic with respect to cancer type," said Patrick Soon-Shiong, M.D., Founder and Executive Chairman of ImmunityBio. "We hope to see durable benefit as the study progresses, which would suggest that Anktiva can confer long-term re-sensitization of tumor tissue to checkpoint inhibitor therapy across several cancer types and patterns of patient history."

Human solid tumors are made of multiple clones of tumor cells, some of which harbor genomic alterations that make them invisible to T cells. These resistant clones accomplish this "cloaking ability" by preventing the presentation of the tumor antigens on MHC-I receptors, thus "hiding" from killer T cells. For these patients, maximum activation of T cells with immunotherapy is unlikely to lead to durable tumor control or a cure. However, when NK cells are activated, tumor recognition and targeting is restored. Anktiva activates both NK and T cells and a potential mechanism of rescuing patients from checkpoint relapse is the administration of Anktiva together with the same checkpoint therapy.

"We hypothesize that checkpoint therapy alone is insufficient and that the combination of Anktiva with or without PD-L1 t-haNK may advance the strategy of developing a chemotherapy free immunotherapy protocol for the treatment of multiple tumors. We have previously demonstrated that PD-L1 t-haNK plays an important role in checkpoint failures. The encouraging data from this Phase 2 exploratory trial has formed the basis of our randomized Phase 3 clinical trials in lung cancer (QUILT 2.023, NCT03520686)" said Dr. Soon-Shiong.

Study highlights to date include:

140 patients with checkpoint relapse accrued across multiple tumor types: NSCLC, Small Cell, Urothelial, Head & Neck, Melanoma, Renal, Gastric, and Cervical cancer
121 evaluable patients to date with preliminary data demonstrating 68% (82 out of 121) disease control (partial response and stable disease >6 weeks)
Anktiva exhibits a favorable toxicity profile in combination with several different checkpoint inhibitors in second-line or greater settings, across a variety of tumor types
Adverse events, 12% of which were grade 3 or above, that were related to the chemotherapy-free combination regimen were favorable to the historical standard of care comprising combination therapies that include chemotherapy
Treatment-related serious adverse events (SAEs) were seen in 8% of study participants
Combination regimens that included Anktiva demonstrated clinical benefit in the majority of subjects, with cessation of progression, prolonged stable disease, and occasional partial responses per RECIST were observed in different tumor types