NantKwest announced Tuesday that a patient with metastatic pancreatic cancer achieved a complete response when treated with the company's off-the-shelf, PD-L1 tumour-targeted natural killer (NK) cells, dubbed PD-L1.t-haNK, in combination with ImmunityBio's IL-15 fusion protein N-803. The results were detailed by NantKwest CEO Patrick Soon-Shiong at the J.P. Morgan Healthcare Conference, sending the drugmaker's shares up as much as 91%.
The patient took part in a Phase I trial involving 11 subjects with metastatic pancreatic cancer who had received NantKwest's antibody-targeted NK cells, known as haNK, and N-803. Soon-Shiong said the first 10 patients in the study had achieved partial responses. However, based on safety and efficacy data from the trial, an expanded access regimen was authorised to treat the patient in question with a combination of N-803 and PD-L1.t-haNK, an advanced form of NantKwest's therapy that was engineered to target the PD-L1.
After five infusions, NantKwest said the patient's tumour metastasis "resolved completely" as seen on computed tomography (CT) and positron emission tomography (PET) scans. The patient continues to receive ongoing treatment.
The findings build on results presented last month at the San Antonio Breast Cancer Symposium (SABCS) in patients with triple-negative breast cancer. Two of nine women treated with a regimen that included NantKwest's haNK cells combined with N-803, as well as Merck KGaA and Pfizer's PD-L1 checkpoint inhibitor Bavencio (avelumab), had ongoing complete responses with durations ranging from eight to 11 months.
Soon-Shiong said more than 300 patients have received the treatment, although he has only shared details on a few of them. Still, he suggested that "these results are important, proof-of-concept supporting our hypothesis that comprehensively activating the immune responses of the NK, T and dendritic cells, the 'triangle' offense, would induce immunogenic cell death leading to durable responses, even among this challenging patient population." Based on the findings, NantKwest plans to initiate clinical trials in second-line metastatic pancreatic cancer and third-line triple-negative breast cancer.
"The evolution of the next generation NK in our platform was now to enable haNK cells to target tumours by expressing PD-L1 CAR on the surface of haNK NK cells," Soon-Shiong said, adding that "these PD-L1.taNK NK cells have the properties of targeting PD-L1 on tumours, without the need of [the] additional PD-L1 checkpoint, Bavencio."
The executive also pointed to recent data presented at the Society for Immunotherapy of Cancer conference (SITC) demonstrating complete responses in third-line Merkel cell carcinoma and fourth-line head and neck cancers when haNK CD-16 NK cells were combined with Bavencio and with N-803.
According to NantKwest, the FDA authorised the first-in-human safety studies of PD-L1.t-haNK at doses of two billion cells administered bi-weekly as outpatients. With no dose-limiting or treatment-related events noted in patients treated to date in the first dosing cohort, NantKwest said the study is now enrolling a dose cohort of four billion cells per infusion.
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