On December 16, 2019 NantKwest Inc. (Nasdaq: NK), a clinical-stage natural killer cell-based therapeutics company, and ImmunityBio, a privately held immunotherapy company, reported results from their Phase 1b trial investigating a novel, first-in-human immunotherapy protocol consisting of NantKwest’s off-the-shelf, antibody-targeted NK cells (haNK) combined with ImmunityBio’s IL-15 superagonist (N-803), low-dose metronomic chemoradiation therapy, adenoviral and yeast tumor-associated antigen vaccines (MUC1, brachyury, CEA) and a PD-L1 checkpoint inhibitor in patients with metastatic triple negative breast cancer (TNBC) who had relapsed after prior therapy (Press release, NantKwest, DEC 16, 2019, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-and-immunitybio-present-results-landmark-trial-first?field_nir_news_date_value[min]=2019 [SID1234552402]).

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The results were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 13, 2019, in San Antonio, Texas, in a poster titled "Safety and efficacy from first-in-human immunotherapy combining NK and T-cell activation with off-the-shelf, antibody-targeted CD16 NK cell line (haNK) in patients with 2nd-line or greater metastatic triple-negative breast cancer (TNBC)."

This landmark study is the world’s first trial to combine cellular therapy with checkpoint inhibitors and IL-15 cytokine stimulation, as well as with adenoviral vectors, all acting in concert to induce immune simulation of both NK cells and T cells.

"We are extremely pleased that the FDA granted us IND authorization to initiate this novel immunotherapy trial enabling the safety and efficacy study of multiple novel biological agents administered as a single protocol in the outpatient setting," said Dr. Patrick Soon-Shiong, Chairman and CEO of NantKwest. "This important trial forms the basis of our approach to induce immunogenic cell death and long-term memory, and avoid the ravages of high dose chemotherapy."

"Achieving durable, complete responses in metastatic TNBC patients that have failed all current standards of care is a promising finding and further validates our approach to orchestrate both the innate and adaptive immune system," continued Soon-Shiong. "TNBC is a highly aggressive cancer, with limited treatment options and poor prognosis. These results are important proof-of-concept supporting our hypothesis that comprehensively activating the immune responses of the NK, T and Dendritic cells would induce immunogenic cell death leading to durable responses, even among this challenging patient population. We are thrilled with the safety and efficacy data from this first-in-human clinical trial of combination NK cell therapy, cytokine fusion protein, chemoradiation and checkpoint inhibitor, and look forward to advancing this exciting off-the-shelf cell therapy approach to randomized clinical trials in this setting."

Data Highlights Include:

Of 9 patients treated, efficacy results include a disease control rate of 78% (7/9 patients) and an overall response rate of 67% (6/9 patients).
2 out of 9 patients to date have ongoing complete responses with durations ranging from 8 to 11 months, with a 3rd patient demonstrating a partial response (near complete response) in the target lesion after initiation of targeted and endocrine therapy off-study.
To date, 7 patients are alive with durations of response ranging from 2 to 12 months with 4 patients remaining on study. Median progression-free survival rate is 13.7 months.
All patients were treated in an outpatient setting with treatment generally safe and well tolerated and no observed cytokine release syndrome.
No immune related SAEs were attributed to the immunotherapy investigational agents
All patients had at least 1 grade ≥ 3 TRAE, primarily chemotherapy-related neutropenia or anemia. Grade ≥ 3 haNK-related AEs, namely fever and fatigue, were observed in 2 patients.
Early data from peripheral blood analysis demonstrate clonal selection occurs with the immunotherapy regimen enabling targeted therapy tailored to patient specific mutations identified via next generation sequencing.
"The approximately 10-20% of breast cancer patients who are triple negative are faced with a grim prognosis with limited treatment options. These results are clinically significant, with overall response rates and complete response rates in this highly refractory, advanced metastatic patient population," said Dr. Chaitali Nangia, a Hematologist/Oncologist with the Chan Soon-Shiong Immuno-Oncology Network and study co-author. "Importantly, these responses to treatment are also durable, with median progression free survival exceeding 13 months compared to historical controls of approximately 3 months in this heavily pretreated population. We also observed a positive safety and tolerability profile, with no cytokine release syndrome. Taken together, these efficacy and safety results point to the emergence of a new treatment paradigm for TNBC."