MG4101

For allogeneic natural killer cell therapy, strategies including the use of the high-affinity hFcγRIIIaV158 variant of the KIR B/x haplotype with lymphodepleting chemotherapy could be promising options for improving clinical efficacy in the antibody combination therapeutic setting as an off-the-shelf product. MG4101 plus rituximab presented a favorable safety profile and overall response rate in patients with r/rNHL.

P2, N=12, Terminated, Seoul National University Hospital | Trial completion date: Dec 2022 --> Apr 2022 | Active, not recruiting --> Terminated; Issues in supply of IP

Despite the proven clinical activity of tafasitamab in combination with lenalidomide in the treatment of diffuse large B-cell lymphoma (DLBCL), a higher number of immune cells in cancer patients may improve the activity of tafasitamab. Combination treatment of tafasitamab and allogeneic MG4101 NK cells in these models demonstrated a survival benefit compared with tafasitamab or MG4101 monotherapy (Raji: 1.7- to 1.9-fold increase in lifespan; Ramos: 2.0- to 4.1-fold increase in lifespan). In conclusion, adoptive cell transfer of ex vivo-expanded allogeneic NK or autologous γδ T cells in combination with tafasitamab treatment may potentially be a promising novel approach to increase the number of immune effector cells and enhance the antitumor effect of tafasitamab.

P2, N=12, Active, not recruiting, Seoul National University Hospital | Trial primary completion date: Jan 2022 --> Apr 2022

After lymphodepletion with fludarabine and cyclophosphamide, MG4101 derived from unrelated healthy donors was administered intravenously for 3 days during the first 3 weeks of the treatment cycle followed by IL-2 for 3 days. MG4101 in refractory or relapsed AML was well tolerated without significant treatment-related toxicity. NKRL expression in AML blasts was heterogeneous, and treatment response with MG4101 was also highly variable. In our patient cohort, patients with high activating KIR responded favorably to MG4101 treatment.

P2, N=12, Active, not recruiting, Seoul National University Hospital | Recruiting --> Active, not recruiting | N=28 --> 12 | Trial primary completion date: May 2021 --> Jan 2022

Immunotherapy using ex vivo-expanded allogenic NK cells in hepatectomy patients can be used safely. Further studies should be investigated for efficacy.

P2, N=28, Recruiting, Seoul National University Hospital | Trial primary completion date: May 2020 --> May 2021

Patients received lymphodepleting chemotherapy of fludarabine 20mg/m2/day and cyclophosphamide 250mg/m2/day for three days before the administration of MG4101 at cycle 1, 3, and 5...Conclusion The combination therapy of MG4101 with rituximab is a very tolerable treatment with an encouraging antitumor effect in relapsed or refractory NHL patients with a 55.6% response rate. The updated immunological profile, cytokine production, and survival data will be presented.

The grade 3/4 adverse events possibly related to MG4101 were hematologic toxicities including neutropenia (n=3) and febrile neutropenia (n=1), which occurred within 2 weeks after lymphodepeltion suggesting those G3/4 toxicities are more likely due to fludarabine/cyclophosphamide rather than MG4101...Conclusion This clinical study has demonstrated that the combination treatment of MG4101 with rituximab is feasible with favorable safety profile and encouraging response rates in relapsed or refractory NHL patients. Safety and efficacy data with longer follow-up will be updated.