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B-NHL Cell Therapy Cleared for Trials

Oncternal will soon initiate a phase 1/2 dose-escalation study of ONCT-808.

The FDA has granted investigational new drug (IND) clearance for a phase 1/2 dose escalation study of Oncternal Therapeutics’ chimeric antigen receptor (CAR) T therapy ONCT-808 for treating aggressive B cell non-Hodgkin’s lymphoma (B NHL).1

“We are very pleased with the clearance of our IND application for our lead autologous CAR T product candidate, ONCT-808,” James Breitmeyer, MD, PhD, president and chief executive officer, Oncternal, said in a statement.1 “This will be our second clinical program focusing on the important ROR1 cancer target, following the initiation of our phase 3 study for our ROR1 antibody zilovertamab, announced last week.”

ONCT-808 is an autologous CAR T therapy that targets ROR1. The study will enroll patients with aggressive B NHL, including those whose disease has been refractory to previous CD19 CAR T treatment.

“ROR1 is an exciting and promising target that is highly expressed in a wide range of cancers and is an ideal candidate for cell therapy applications due to its highly specific tumor expression, and association with tumor survival mechanisms. Our initial dose finding study will enroll patients with aggressive B NHL, including those that have failed prior CD19 therapy, which represent a significant unmet need in the market today. We expect to initiate the study in the coming months and to present interim results at a scientific conference in 2023,” Breimeyer added.1

READ MORE: Allogeneic CAR T Recognized for Cutaneous T-Cell Lymphomas

Oncternal previously presented positive preclinical data on ONCT-808 at the European Hematology Association (EHA) 2022 Hybrid Congress in June 2022.1 The data were from preclinical studies conducted by Oncternal’s collaborator, the Karolinska Institute in Stockholm. The data presented demonstrated ROR1 CAR mediated target recognition and cell activation when expressed in either T cells or NK cells. Also, ROR1 CAR-T cells demonstrated dose-dependent anti-tumor activity in a mantle cell lymphoma mouse model.

Oncternal’s lead programs are zilovertamab, a monoclonal antibody that inhibits ROR1, which is in phase 2 trials, primarily for mantle cell lymphoma, and ONCT-216, a small molecule inhibitor of ETS-family oncoproteins, which is in phase 2 studies, primarily for Ewing sarcoma. Also in the pipeline is the preclinical Dual-Action Androgen Receptor Inhibitor (DAARI) ONCT-534for advanced prostate cancer resistant to available therapies.

“Despite recent significant advances in treating hematological malignancies with current CAR-based cell therapies, certain limitations remain, such as treatment failures due to tumor antigen escape, and toxicities including induction of immunodeficiencies like B-cell aplasia. Patients are in need of more effective treatment options” Evren Alici, MD, PhD, associate professor and group leader, Cell and Gene Therapy Group, Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, said in a statement at that time.2 “The ROR1-targeting cell therapies have shown strong activity in our lymphoma models. We are now working with our Oncternal colleagues to evaluate the therapies in models of other tumor indications. With our strong focus on NK cells, we are excited to further study ROR1 CAR-NK cells within our NextGnNK competence center."

”Oncternal’s lead programs are zilovertamab, a monoclonal antibody that inhibits ROR1, which is in phase 2 trials, primarily for mantle cell lymphoma, and ONCT-216, a small molecule inhibitor of ETS-family oncoproteins, which is in phase 2 studies, primarily for Ewing sarcoma. Also in the pipeline is the preclinical Dual-Action Androgen Receptor Inhibitor (DAARI) ONCT-534for advanced prostate cancer resistant to available therapies.

REFERENCES
1. Oncternal Therapeutics receives IND clearance for ONCT-808, its autologous CAR T product candidate targeting ROR1 for the treatment of aggressive B cell lymphoma. News release. Oncternal. October 3, 2022. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-receives-ind-clearance-onct-808-its
2. Oncternal Therapeutics presents new preclinical data from its anti-ROR1 cell therapy collaboration with the Karolinska Institutet at the EHA2022 Congress. News release. Oncternal Therapeutics. June 10, 2022. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-presents-new-preclinical-data-its-anti