The safety and tolerability of ex vivo TKD / IL-2 stimulated, autologous NK cells (ENKASTIM-ev) has previously been demonstrated in patients with metastasized colorectal and non-small cell lung cancer (NSCLC) in a phase I clinical trial.
Based on promising clinical results of the previous study, a multi-center randomized phase II clinical study has been undertaken. The primary objective of this multi-center 'proof-of-concept' trial was to examine whether an adjuvant treatment of patients with Stage IIIb inoperable non small lung cell carcinoma (NSCLC) after platinum-based radio (chemo) therapy 'Standard of Care 'with TKD / IL-2 activated, autologous NK cells is clinically effective. As we have already shown that a membrane Hsp70-positive tumor phenotype is associated with poor clinical outcome, only patients that have membrane Hsp70-positive tumors were recruited into the trial.
The primary endpoint of this study was a comparison of progression-free survival (PFS) of patients treated with ex vivo activated NK cells with that of patients who were treated with radio (chemo) therapy alone. Secondary endpoints in both study groups were overall survival, toxicity, quality-of-life, and biological responses.
The trial demonstrated that ENKASTIM-ev delivered clinical benefit in 5 out of 7 patients (71%; PFS 13 months; including one patient who left the trial after 15 months PFS - see Case Study below), with one complete response. This contrasts with 2 out of 7 patients (28%, median PFS 8 months) deriving clinical benefit from the radio (chemo) therapy alone in the control group (Multhoff et al., 2020). Also of importance was the finding that no significant side-effects were observed.
Clinical Case Study: Non Small Cell Lung Cancer
ENKASTIM-ev followed by second-line PD-1 inhibition has been shown to deliver long-term disease control in a patient with Stage IIIb inoperable non small lung cell carcinoma (NSCLC) after platinum-based radio (chemo) therapy (Kokowski et al., 2019).