NKGen’s Allogeneic Natural Killer Cell Therapy SNK02 Shows Antitumor Activity and Safety When Administered Without Lymphodepletion

Paul Y. Song, MD
Credit: NKGen

NKGen Biotech’s SNK02, an allogeneic natural killer (NK) cell therapy, has shown antitumor activity and safety in updated data from patients with solid tumors treated ina phase 1 clinical trial (NCT05990920).¹ The data were presented at the 6th Annual Allogeneic Cell Therapies Summit 2024, held June 10-12, in Boston, MA.²

In the trial, 6 patients with solid tumors were enrolled for treatment with SNK02, which is comprised of NK cells isolated from the peripheral blood mononuclear cells of healthy donors that are expanded ex vivo.¹ The trial’s protocol calls for SNK02 to be given weekly via intravenous administration, without lymphodepletion, for at least 8 weeks. All 6 patients received the study’s starting dose of 6x10⁹ SNK02 cells.² Of the 6 aforementioned patients, 4 completed at least 8 weekly doses of SNK02, with 1 patient noted to have received 18 consecutive weekly doses and 1 patient noted to have received 12 consecutive weekly doses.¹ With regard to efficacy, NKGen stated that SNK02 showed “some clinical activity against pretreated solid tumors” and that a best objective response of stable disease (SD) defined as a cesation of tumor growth was seen in all 4 of the patients who completed at least 8 weeks of dosing.¹

In terms of safety, SNK02 was characterized as “well-tolerated”. Adverse event (AE) data included data recorded during the first 8 doses for each patient, which totaled 36 doses across the 6 previously mentionedenrolled patients. AEs deemed related to SNK02 included 17 grade 1 AEs, 3 grade 2 AEs, and a single grade 3 case of increased fatigue that was noted to have resolved without intervention a day after appearing. Furthermore, NKGen also pointed out that autoantibodies in the patients seemed to correlate with the occurrence of AEs and to appear around week 5 of dosing. On the other hand, the company highlighted that there did not seem to be any correlation between KIR mismatch or HLA subtyping and AEs or tumor response to SNK01. A single death occurred in the trial, but was considered not related to SNK02.

The 4 patients who achieved SD in the trial included a patient with angiosarcoma who received 18 doses of SNK02 and was noted to show SD through 4 months posttreatment; a patient with leiomyosarcoma who received 12 doses and showed SD through 3 months posttreatment; a patient with endometrial adenocarcinoma who received 8 doses and showed SD through 2 months posttreatment; and a patient with colorectal cancer who received 10 doses and showed SD through 3 months posttreatment.² The patients who did not achieve SD included a patient with pleomorphic sarcoma who received 4 doses of SNK02 and died of respiratory failure caused by lung disease progression and patient with colorectal cancer who received 4 doses and had progressive liver metastases. All 6 patients were noted to have stage IV disease.

“As most of the focus of NK cell therapy has been for liquid tumors with lymphodepletion, we have always believed that lymphodepletion could be detrimental to patients with solid tumors especially those being treated with immune checkpoint inhibitors, monoclonal antibodies or bispecific therapies where a robust immune response is essential,” Paul Y. Song, MD, the chairman and chief executive officer of NKGen, said in a statement.¹ “We therefore set out to develop a commercial scale manufacturing and cryopreservation process which could yield greater than 100,00 doses of SNK02 (cryopreserved enhanced activated allogeneic NK cells) with the idea that large doses could be delivered without lymphodepletion to potentially overcome any host versus graft reaction. We are pleased to show that, despite developing autoantibodies to sustained repeated dosing of our allogeneic product, SNK02 was safe and treatment appeared to stop the progression of several heavily pretreated solid tumors as a monotherapy. We are excited to further explore the efficacy of SNK02 in combination with immune checkpoint inhibitors and antibodies against solid tumors.”

NKGen originally announced dosing of the first patient in the trial in August 2023.³ According to the clinicaltrials.gov page, which was most recently updated on March 1, 2024, the multicenter, open-label, dose-escalation trial was open to patients with any type of refractory cancer, although the company notes an emphasis on solid tumors. The study’s primary end points are the number of participants who experience dose-limiting toxicities, the maximum tolerated dose and/or ready for phase 2 dose, and the number of participants who experience treatment-related adverse events. The trial is noted to be active, but no longer recruiting new patients, with an "actual enrollment" of 6 participants.

REFERENCES
1. NKgen Biotech presents updated phase 1 data on SNK02 allogeneic NK cell therapy for solid tumors at the 6th annual allogeneic cell therapies summit 2024. News release.NKGen Biotech, Inc. June 12, 2024. Accessed June 17, 2024. https://nkgenbiotech.com/nkgen-biotech-presents-updated-phase-1-data-on-snk02-allogeneic-nk-cell-therapy-for-solid-tumors-at-the-6th-annual-allogeneic-cell-therapies-summit-2024/
2. Song PY. SNK02 : Cryopreserved allogeneic enhanced natural killer cells. Presented at: the 6th Annual Allogeneic Cell Therapies Summit 2024, held June 10-12, in Boston, MA.
3. NKGen Biotech, Inc. announces first patient dosed in phase I clinical trial of SNK02, allogeneic NK cell therapy product candidate, for the treatment of solid tumors. News release. NKGen Biotech, Inc. August 24, 2023. Accessed June 17, 2024. https://nkgenbiotech.com/nkgen-biotech-inc-announces-first-patient-dosed-in-phase-i-clinical-trial-of-snk02-allogeneic-nk-cell-therapy-product-candidate-for-the-treatment-of-solid-tumors/