|eFFECTOR Therapeutics, Inc. recently announced that it has dosed the first patient in the Phase 2 expansion portion of its monotherapy trial of eFT508, the company’s oral, small molecule inhibitor of MNK1/2, for the treatment of relapsed, refractory non-germinal center B cell (non-GCB) diffuse large B cell lymphoma (DLBCL). Non-GCB DLBCL is an aggressive form of non-Hodgkin’s lymphoma that is driven in part by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and frequently responds poorly to standard treatments. The company also announced that it has selected 200 mg eFT508 taken twice daily as the dose for the Phase 2 expansion, as established in the Phase 1 dose-escalation portion of the trial.
“This Phase 2 expansion cohort builds on our Phase 1 results, where we observed a confirmed partial response in one of two non-GCB DLBCL patients enrolled during dose escalation,” said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. “Patients with non-GCB DLBCL who have failed other available treatment options face a devastating disease. We are hopeful that our approach of regulating translation by inhibiting MNK1/2, which lies downstream of NFkB signaling, will be effective in treating these patients in great need of new therapeutic approaches.”
The Phase 2 expansion portion is part of an ongoing Phase 1/2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics and antitumor activity of eFT508 in patients with hematological malignancies [NCT02937675]. The primary endpoint of the expansion cohort is the objective response rate (ORR) of eFT508 in non-GCB DLBCL patients. eFT508 has received orphan drug designation from the FDA for the treatment of DLBCL.
eFT508 is a selective translation regulator and is part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. eFT508 is a highly potent and selective, oral inhibitor of MNK1 and MNK2 (MNK1/2). MNK1/2 are terminal kinases in key oncogenic signaling pathways, including KRAS-BRAF-MEK-ERK, and are activated by the mitogen dependent protein kinases (MAPK) in multiple immune cell types. MNK1/2 integrate MAPK pathway signaling at the level of mRNA translation, resulting in decreased anti-tumor immune activity due to selective upregulation of several immune checkpoint receptors and specific immunosuppressive cytokines. eFT508 selectively blocks MNK1/2 driven mRNA translation, thereby promoting anti-tumor immune response. In addition to the trial in non-GCB DLBCL, eFT508 is being evaluated in a Phase 2 clinical trial in combination with avelumab, an anti-PD-L1 checkpoint inhibitor, in relapsed or refractory microsatellite stable colorectal cancer (MSS CRC) [NCT03258398].
About Diffuse Large B Cell Lymphoma
Diffuse large B cell lymphoma is an aggressive form of non-Hodgkin lymphoma (NHL) that can begin in lymph nodes and areas of the body outside of the lymphatic system. DLBCL is the most common form of NHL, making up 30 percent of newly-diagnosed NHL cases each year, according to the Lymphoma Research Foundation. Due to the fast-acting and aggressive nature of the disease, DLBCL requires immediate treatment upon diagnosis. The non-GCB segment of DLBCL represents tumors that are driven in part by activation of the transcription factor NFkB. Several NFkB-driven messenger RNAs that are critical in non-GCB DLBCL require MNK1/2 to be effectively translated.
About eFFECTOR Therapeutics
eFFECTOR Therapeutics is a clinical-stage biopharmaceutical company focused on pioneering the discovery and development of selective translation regulators as a new class of oncology drugs. The company’s investigational compounds are designed to restore the translational control of processes which tumors have hijacked for their benefit, while preserving normal cell function. eFFECTOR’s most advanced program focuses on the development of eFT508, a MNK1/2 inhibitor in development for the treatment of patients with solid tumors and lymphoma. The company has additional selective translation regulator programs currently in discovery and development and maintains global rights to all of its development programs. For more information visit www.effector.com.