Benzinga | Jan 28, 2021 09:06AM EST

NantKwest Merger Partner ImmunityBio Announces Phase 2 Trial Results Showing 'Anktiva Restores the Activity of Checkpoint Inhibitors in Patients Who Have Relapsed Checkpoint Immunotherapy in Non-Small Cell Lung Cancer'

* Clinical benefit observed in majority of NSCLC patients who progressed on checkpoint inhibitor

* Anktiva(tm) (also called N-803) restored or enhanced activity of checkpoint therapy even in those who progressed on the same checkpoint

* Activity observed regardless of PD-L1 status and prior response to checkpoint inhibitor therapy

* Anktiva combination therapy with checkpoint inhibitors is well tolerated with low incidence of adverse events and could potentially serve as the backbone to all checkpoint inhibitor therapies

ImmunityBio, Inc., a privately held immunotherapy company, today announced the presentation of encouraging data in non-small cell lung cancer (NSCLC) from the company's ongoing Phase 2b study, QUILT-3.055 (ClinicalTrials.gov: NCT03228667) at the International Association for the Study of Lung Cancer (IASCL)'s 2020 World Conference on Lung Cancer, Singapore, being held virtually January 28 -- 31, 2021.

The presentation, titled "QUILT 3.055: a phase 2 multi-cohort study of N803 (IL-15 superagonist) in combination with checkpoint inhibitors in NSCLC," highlighted safety and efficacy data from NSCLC patients in Cohort 1 of the study (N=78), which is evaluating patients with initial response on single-agent checkpoint inhibitor therapy who subsequently progressed on or after that therapy in multiple tumor types. The study is designed to evaluate combination immunotherapy regimens that include ImmunityBio's lead cytokine infusion protein, a novel interleukin-15 (IL-15) superagonist complex (Anktiva(tm), also called N-803) in patients who have previously received treatment with PD-1/PD-L1 immune checkpoint inhibitors. 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 presentation results include:

* Clinical benefit was demonstrated in a majority of the NSCLC patients, as measured by reduction of target lesion size and cessation of progression in the target lesion over time (with follow-up of up to 13 months).

* Clinical benefit was observed in patients with immediate prior progression on checkpoint inhibitors when Anktiva was combined with the checkpoint inhibitor, regardless of PD-L1 status or use of chemotherapy with checkpoint inhibitors

* The combination regimen of Anktiva and checkpoint inhibitors was well tolerated, with low incidence of treatment-related severe adverse events in second- and third-line NSCLC patients who had progressed on checkpoint inhibitor therapy at the time of study enrollment.

* Among 78 participants, nine (12%) exhibited grade 3 or higher treatment-emergent adverse events (AEs). Common low-grade AEs observed included injection site reactions (72%), chills (30%), fatigue (27%), fever (26%) and nausea (12%).

* These results suggest that a combination regimen with Anktiva has the potential to restore and or enhance responsiveness to checkpoint inhibitors, including in patients with low PD-L1 expression, which typically is a robust predictor of checkpoint inhibitor failure.

"These encouraging safety and efficacy data suggest that the addition of Anktiva to checkpoint inhibitors has the potential to restore and/or enhance sensitivity to checkpoint inhibitors. While immunotherapy has been transformative for many NSCLC patients, particularly those with high PD-L1 expression, the majority will not experience durable response to these treatments," said lead investigator John Wrangle, M.D., Associate Professor, Division of Hematology/Oncology at Hollings Cancer Center at the Medical University of South Carolina. "Strikingly, we see clinical benefit in patients with immediate prior progression on checkpoint inhibitors and low PD-L1 expression, groups which historically are less likely to respond to checkpoint inhibitors, without the need for interval chemotherapy or radiation therapy and their attendant toxicities."

Tumor resistance to checkpoint therapy occurs when T cells are unable to recognize the tumor cell antigen. NK cells can overcome this resistance as indicated by Allen, et al., "Mechanisms of resistance to T cell-based immunotherapy in head and neck cancer" (DOI: 10.1002/hed.26158), who show that NK cells can improve the efficacy of T-cell activated immunotherapy such as checkpoint inhibitors.

Sandeep Bobby Reddy, M.D., Chief Medical Officer at ImmunityBio, commented, "This Phase 2 study demonstrates that activation of NK cells through administration of Anktiva, reactivates and restores the activity of checkpoint inhibitor therapy even in patients who relapsed on the same checkpoint therapy. Thus, the potential exists that Anktiva could be the combination backbone to all checkpoint therapy by activating both NK and T cells. We believe that our particular approach in using an engineered IL-15 superagonist to coordinate T cell and natural killer cell-mediated responses may elicit tumor response, regardless of the type and extent of prior checkpoint inhibitor therapy, PD-L1 status, and tumor type. The data presented are from the NSCLC cohort of a multi-cohort ongoing trial in 11 checkpoint inhibitor indications. Much excitement has been generated with targets such as TIGIT, OX40, TIM3, LAG3 and many others. We are particularly excited that our approach is independent of a particular biomarker and may have a broader applicable patient population."

Lung cancer is the second most common cancer in men and women (excluding skin cancer), and non-small cell lung cancer accounts for 80% to 85% of all lung cancers, according to the American Cancer Society. In 2021, more than 235,000 people will be diagnosed with lung cancer and more than 131,000 people will die from the disease.