MG4101 / GC Biopharma - LARVOL DELTA

MG4101, an allogeneic natural killer cell, in patients with relapsed or refractory acute myeloid leukemia: a pilot study. (PubMed, Leuk Lymphoma) - "The sum of activating KIRs in responders tended to be higher than that in non-responders. Analyses of NKRL and KIR highlighted the importance of immunological mechanisms in treating myeloid neoplasms."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

MG4101 for Refractory or Relapsed AML (clinicaltrials.gov) - P2 | N=11 | Completed | Sponsor: Seoul National University Hospital | Unknown status ➔ Completed

Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Functional Characterization of Gamma Delta T Cells and Allogeneic Activated NK Cells As Effector Cells for Tafasitamab (MOR208) (ASH 2019) - "Tafasitamab is currently in clinical development in patients with relapsed or refractory DLBCL in combination with the immunomodulatory drug lenalidomide (L-MIND study) and the chemotherapeutic agent bendamustine (B-MIND study)...Methods γδ T cells (CD3+/γδ T cell receptor+) were derived from different donors by stimulation of peripheral blood mononuclear cells with zoledronate/IL-2 for 9–10 days...Combination therapy with tafasitamab and allogeneic MG4101 NK cells in vivo demonstrated a more than additive survival benefit compared with tafasitamab or MG4101 monotherapy in a disseminated therapeutic lymphoma model. Combination of tafasitamab supplemented with immune effector cells could represent a promising new approach for lymphoma therapy."

IL2

Phase I study: safety and efficacy of ex vivo-expanded allogeneic natural killer cells (MG4101) with rituximab for relapsed/refractory B-cell non-Hodgkin lymphoma. (PubMed, Transplant Cell Ther) - "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."

Journal • P1 data • Preclinical • Hematological Malignancies • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL2

Rituximab Plus MG4101 Indolent CD20-positive Non-Hodgkin Lymphoma (NHL) (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: Seoul National University Hospital | Trial completion date: Dec 2022 ➔ Apr 2022 | Active, not recruiting ➔ Terminated; Issues in supply of IP

Trial completion date • Trial termination • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

A Pilot Study of MG4101, Allogeneic Natural Killer Cell, in Patients with Relapsed or Refractory Acute Myeloid Leukemia (ASH 2021) - "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."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • NKG2D • PD-L1

Tafasitamab mediates killing of B-cell non-Hodgkin's lymphoma in combination with γδ T cell or allogeneic NK cell therapy. (PubMed, Cancer Immunol Immunother) - "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."

Combination therapy • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Rituximab Plus MG4101 Indolent CD20-positive Non-Hodgkin Lymphoma (NHL) (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Seoul National University Hospital | Trial primary completion date: Jan 2022 ➔ Apr 2022

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Rituximab Plus MG4101 Indolent CD20-positive Non-Hodgkin Lymphoma (NHL) (clinicaltrials.gov) - P2; N=12; Active, not recruiting; Sponsor: Seoul National University Hospital; Recruiting ➔ Active, not recruiting; N=28 ➔ 12; Trial primary completion date: May 2021 ➔ Jan 2022

Enrollment change • Enrollment closed • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

[VIRTUAL] FEASIBILITY OF ALLOGENEIC NATURAL KILLER CELLS, MG4101 IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH RELAPSED OR REFRACTORY NON-HODGKIN LYMPHOMAS; A PHASE 1, OPEN-LABEL, MULTICENTER STUDY (EHA 2020) - "Patients were subjected to a lymphodepleting chemotherapy consisting of fludarabine (25 mg/m2) and cyclophosphamide (250mg/m2) on days -3 to -1 before the first administration of rituximab and MG4101 of the 1st, 3rd, and 5th cycles. 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."

Clinical • Combination therapy • P1 data • Diffuse Large B Cell Lymphoma • Fatigue • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hypotension • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • IL2

[VIRTUAL] A Phase 1 Study of the Combination of MG4101, Ex Vivo-Expanded Allogeneic NK Cells and Rituximab for Relapsed or Refractory Non-Hodgkin Lymphoma (ASH 2020) - P1/2 | "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."

P1 data • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hypotension • Immunology • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • IFNG • IL2 • NCAM1 • PCR

Adjuvant therapy using ex vivo-expanded allogenic natural killer cells in hepatectomy patients with hepatitis B virus related solitary hepatocellular carcinoma: MG4101 study. (PubMed, Ann Hepatobiliary Pancreat Surg) - P2 | "Immunotherapy using ex vivo-expanded allogenic NK cells in hepatectomy patients can be used safely. Further studies should be investigated for efficacy."

Journal • Preclinical • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD8

Mutations introduced in susceptibility genes through CRISPR/Cas9 genome editing confer increased late blight resistance in potatoes. (PubMed, Sci Rep) - "Additionally, we showed that DMG401026923 (here denoted StDMR6-2) knockout mutants did not demonstrate any increased late blight resistance, but exhibited a growth phenotype, indicating that StDMR6-1 and StDMR6-2 have different functions. To the best of our knowledge, this is the first report on the mutation and screening of putative S-genes in potatoes, including two DMR6 potato homologues."

Journal

Rituximab Plus MG4101 Indolent CD20-positive Non-Hodgkin Lymphoma (NHL) (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: Seoul National University Hospital; Trial primary completion date: May 2020 ➔ May 2021

Clinical • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

MG4101 Plus Rituximab Including Lymphodepletion in Patient With r/r NHL B-cell Origin (clinicaltrials.gov) - P1/2; N=9; Active, not recruiting; Sponsor: Green Cross LabCell Corporation; Recruiting ➔ Active, not recruiting; N=100 ➔ 9; Trial completion date: Dec 2022 ➔ Oct 2020

Clinical • Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

GC LabCell releases clinical results of NK cell therapy (Korea Biomedical Review) - P1/2, N=100; NCT03778619; Sponsor: Green Cross LabCell Corporation; "Studies on patients with lymphoma have shown excellent interim results in the efficacy and safety of the combination therapy of MG4101 and Rituximab. As a result of the administration, 50 percent of all patients showed a partial response, and there were no side effects such as dose-limiting toxicity."

P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

MG4101 Plus Rituximab Including Lymphodepletion in Patient With r/r NHL B-cell Origin (clinicaltrials.gov) - P1/2; N=100; Recruiting; Sponsor: Green Cross LabCell Corporation; Trial primary completion date: Oct 2019 ➔ Apr 2020

Clinical • Combination therapy • Trial primary completion date

GC Labcell releases trial results of NK-cell combination treatment (Korea Biomedical Review) - "GC Labcell has presented the preclinical trial data for new blood cancer treatment that combines its MG4101, a natural killer (NK) cell treatment, and Tafasitamab, a targeted-anticancer treatment developed by MorphoSys....'Animal studies confirmed increased antibody-dependent cellular cytotoxicity (ADCC) compared to the monotherapy of each agent.'"

Preclinical

Rituximab Plus MG4101 Indolent CD20-positive Non-Hodgkin Lymphoma (NHL) (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: Seoul National University Hospital; Not yet recruiting ➔ Recruiting; Trial completion date: Jul 2021 ➔ Dec 2022; Trial primary completion date: May 2019 ➔ May 2020

Clinical • Enrollment open • Trial completion date • Trial primary completion date

A Study of MG4101 (Allogeneic Natural Killer Cell) for Intermediate-stage of Hepatocellular Carcinoma (clinicaltrials.gov) - P2a; N=78; Completed; Sponsor: Green Cross LabCell Corporation; Recruiting ➔ Completed; Trial completion date: Jun 2018 ➔ Sep 2019; Trial primary completion date: Feb 2018 ➔ Sep 2018

Clinical • Trial completion • Trial completion date • Trial primary completion date

GC Labcell releases pre-clinical trial results for NK cell treatment (Korea Biomedical Review) - “GC Labcell said that it has published the pre-clinical trial results for MG4101, a natural killer (NK) cell treatment of pancreatic cancer, in an international journal….Pancreatic cancer’s animal model confirmed MG4101’s antitumor efficacy after showing a high tumor inhibition rate compared to Gemcitabine.”

Preclinical