On June 5, 2023 NKGen Biotech Inc. (NKGen), a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic and CAR-NK Natural Killer (NK) cell therapeutics, reported a poster presentation of preclinical and Phase I/IIa clinical data by its parent company, NKMax Co., Ltd. (NKMax) (Press release, NKMax America, JUN 5, 2023, View Source [SID1234632518]). The poster titled "The safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: Preclinical mouse model and phase I/IIa clinical study" was presented on June 4th at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The SNK01 program continues to show positive progress, with the most recent preclinical and Phase I/IIa clinical data presented at ASCO (Free ASCO Whitepaper)," said Paul Y. Song, M.D., Chief Executive Officer of NKGen. "Lung adenocarcinoma accounts for nearly 40% of all non-small cell lung cancers (NSCLC) and represents the fastest growing subtype of lung cancer worldwide, especially among non-smoking women. Approximately 15-25% of lung cancer patients diagnosed in the U.S., and up to 50% of patients in Asia, will have an EGFR-positive mutation. While Tyrosine Kinase Inhibitors (TKIs) have shown tremendous efficacy in the front-line setting, salvage regimens have proven to be far less effective in TKI resistant disease. No SNK01-related adverse event of Grade 3 or higher was observed when autologous natural killer cells (SNK01) were delivered in combination with cytotoxic chemotherapy, including cetuximab. The data also demonstrated antitumor activity in both a cell-derived TKI resistant xenograft (CDX) mouse model and in patients with EGFR-mutated non-small cell lung cancer who failed prior TKI treatment. The results of this study are promising and warrant further evaluation. We are excited about the potential therapeutic benefits of SNK01, particularly in this growing population of refractory patients with difficult-to-treat cancers."
In the preclinical study, a humanized CDX mouse model with functional human immune system using an osimertinib-resistant lung cancer cell line was established. Mice were divided into four groups based on treatment (no treatment [n=2]; cetuximab monotherapy [n=3]; SNK01 monotherapy [n=4]; SNK01 in combination with cetuximab [n=4]) and treated weekly for five weeks (SNK01, 1×107 cells/dose; cetuximab, 20 ug/dose). Tumors were tracked weekly through an in vivo imaging system and extracted after completion of treatment. Flow cytometric analysis showed that NK cells (CD45+/CD56+/CD3-) were significantly increased in the groups administrated SNK01, while cytotoxic T cells (CD45+/CD3+/CD8+) in the cetuximab group decreased. The volume of tumor extracted after completion of treatment was the smallest in SNK01 plus cetuximab group.
In the Phase I/IIa dose-escalation clinical trial (ClinicalTrials.gov Identifier: NCT04872634), 12 patients with EGFR-mutated NSCLC who failed prior TKI treatment were enrolled and received weekly infusions of SNK01 for seven or eight weeks (4×109 cells/dose [n=6]); or 6×109 cells/dose [n=6]), SNK01 combination with gemcitabine/carboplatin (n=6) or gemcitabine/carboplatin/cetuximab (n=6). This trial was designed as dose-escalation of SNK01 following a "3+3" design. The primary and secondary endpoints were safety and efficacy, respectively. Median age of patients was 61 years, 33.3% were male, and all patients had lung adenocarcinoma. Dose-limiting toxicity was not observed, therefore the maximum tolerated dose of SNK01 was determined to be 6×109 cells/dose. No SNK01-related adverse events of Grade 3 or higher were observed. The objective response rate was 25% (3/12), disease control rate (DCR) was 100%, with 3/12 patients experiencing a partial response (25%) and 9/12 with stable disease (75%). Median progression free survival (PFS) was 143 days. Some patients are still being followed and an updated PFS will be provided at a later date.