Off-the-shelf natural killer cells safe, clinically active for advanced Merkel cell carcinoma
NATIONAL HARBOR, Md. — Allogeneic activated natural killer cell therapy resulted in some antitumor activity with no serious side effects in patients with metastatic Merkel cell carcinoma, according to the results of a phase 2 study presented at the SITC Annual Meeting.
Participants received activated NK cell therapy alone and in combination with N-803 during the QUILT-3.009 trial; researchers observed clinical antitumor activity in both treatment groups.
N-803 (NantKwest) is an investigational superagonist fusion complex of the cytokine interleukin-15 that enhances binding to the IL-2 receptor.
“Merkel cell carcinoma is a rare but aggressive skin cancer with a high metastatic potential which has very treatment options after having progressed on, or relapsed after treatment with an anti-PD-1 or anti-PD-L1 antibody,” Sunandana Chandra, MD, assistant professor of medicine at Northwestern University Feinberg School of Medicine, told Cell Therapy Next.
“This was one of the first trials in Merkel cell carcinoma that used natural killer cells, which are key effector cells of the innate immune system that mediate antitumor and antivirus immunity,” Chandra added.
Investigators enrolled seven patients into the study, with three patients receiving activated NK cell monotherapy and four patients receiving activated NK cells plus N-803.
All study patients (median age 63 years; range 60-81; 86% men) had inoperable stage III or IV MCC.
Activated NK cells (aNK cells) came from a male patient with rare NK-cell lymphoma; they underwent on-site expansion and were irradiated before IV administration into study patients.
Two of seven patients showed a response to treatment, for an objective response rate (ORR) of 29%. One patient in the aNK cell monotherapy group had a radiologic complete response, and one patient in the combination therapy group had a partial response to treatment. One patient in the combination therapy group had stable disease that lasted 5.5 months.
“Historically, patients with Merkel cell carcinoma had very few options, such as chemotherapy or palliative radiation after progressing on PD-1 axis drugs (anti-PD-1 antibody or anti-PD-L1 antibody),” Chandra said. “The QUILT-3.009 trial, albeit a small trial, exhibited that further therapy with aNK cells in addition to N-803 can lead to ORR of 29%, and perhaps more importantly, may lead to durable responses in some cases.”
There were no serious (grade 3 or greater) treatment-related adverse events in either treatment arm during phase 2 of the QUILT-3.009 trial; the treatment was well tolerated as an outpatient therapy, according to the investigators.
There were five grade 3 or greater adverse events (peripheral edema, sepsis, hydronephrosis, ureteric compression and ureteric obstruction); none of these were considered to be related to the study drug. The most common adverse events (grade 2) were chills (75%) and injection site erythema (75%).
“This trial showed that activated NK cells given in combination with N-803 not only had an acceptable safety and tolerability profile but led to the reversal of PD-1 refractoriness in the case of one patient. Preliminary data show an increased CD8+T cell infiltration and increased IFN-gamma signature after activated NK cell therapy,” Chandra said.
“This trial was one of the first of its’ kind to show that activated NK cells, in addition to CD8+ T cells, may have therapeutic benefit in Merkel cell patients.” – by Drew Amorosi
Bhatia S, et al. Abstract O19. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 7-10, 2019; National Harbor, MD.
Disclosures: Chandra reports consulting and advisory board roles with Array BioPharma, Bristol-Myers Squibb, EMD Serono and Regeneron.