On December 2, 2019 NantKwest, Inc. (Nasdaq: NK), a clinical-stage natural killer cell-based therapeutics company, reported promising safety data generated from the first six patients in its QUILT-3.064 trial (Press release, NantKwest, DEC 2, 2019, View Source [SID1234551840]). The first-in-human study evaluated the safety and preliminary efficacy of the Company’s first-in-class, tumor-targeted PD-L1.t-haNK cell therapy in patients with locally advanced or metastatic solid tumors.

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"The unique dual-targeting of PD-L1.t-haNK to both PD-L1 expressing tumors and therapeutic monoclonal antibodies has the potential to be transformative to the treatment of advanced solid tumors with cell-based therapies," said Dr. Patrick Soon-Shiong, the Chairman and CEO of NantKwest. "PD-L1.t-haNK is a cryopreserved, off-the-shelf product that can rapidly deliver treatment to patients in an outpatient setting while avoiding the extensive manufacturing delays associated with autologous CAR-T therapies. We look forward to reporting full study results from the phase 1 cohort and moving toward a recommended phase 2 dose. We continue to advance our innovative cell therapies such as PD-L1.t-haNK in combination with ImmunityBio’s N-803, an IL-15 superagonist that is designed to stimulate the activation and proliferation of the patient’s own NK cells to maximize the potential of immunogenic cell death to treat cancer," continued Soon-Shiong. NantKwest and a wholly owned subsidiary of ImmunityBio have entered into an exclusive collaboration agreement to co-develop NantKwest’s proprietary off-the-shelf NK platforms in combination with N-803.

On December 2, 2019 at the NantKwest Key Opinion Leader and Investors conference, Dr. Soon-Shiong described the clinical development plans for two of NantKwest’s first-in-class NK products: haNK, which was developed to target binding to approved monoclonal therapies such as Trastuzumab, Rituximab and Cetuximab; and PD-L1.t-haNK, which was also designed to target these approved therapies plus directly target PD-L1-expressing tumor cells.

PD-L1.t-haNK cells are a human-derived, allogeneic, natural killer cell line engineered to express a chimeric antigen receptor (CAR) targeting PD-L1, whose origins arise from NantKwest’s proprietary NK-92 (aNK) master cell bank. In addition to targeting PD-L1, PD-L1.t-haNK is engineered to produce intracellular IL-2 for enhanced CD16-targeted antibody-dependent cellular cytotoxicity capabilities.

John Lee, M.D., Clinical Senior Vice President at NantKwest, said, "We are highly encouraged by the early safety results with PD-L1.t-haNK in a patient population with advanced, difficult to treat solid tumors. All patients were able to be infused in the outpatient setting without any reported cytokine toxicities or immune related adverse events. NantKwest’s approach has been designed to overcome the challenges and limitations typically seen when treating solid tumors with CAR-T and other immunotherapy approaches and I look forward to progressing our studies to advance this innovative new approach to cancer therapy."

Study Design

The QUILT-3.064 study is an open-label, Phase 1 study of PD-L1.t-haNK in subjects with locally advanced or metastatic solid cancers to evaluate safety, preliminary efficacy, determine maximum tolerated dose (MTD) or highest tolerated dose (HTD) and designate the recommended Phase 2 dose (RP2D). The study is being conducted in two parts: the first is evaluating dose escalation using a 3 + 3 design and the second part will evaluate the expansion of the recommended Phase 2 dose (RP2D) to further assess the safety and efficacy of PD-L1.t-haNK therapy. In part one, six subjects were sequentially enrolled, starting at dose level 1 and assessed for dose-limiting toxicities. The primary study objectives are to determine the MTD or HTD, RP2D (recommended phase 2 dose), and safety. The secondary endpoints include objective response rate (ORR), progression free survival (PFS) and overall survival (OS). More information can be found at ClinicalTrials.gov, Identifier: NCT04050709.