Oncternal Therapeutics has decided to discontinue its Phase 1/2 ONCT-808-101 clinical trial evaluating ONCT-808, an investigational autologous CAR-T therapy, for the treatment of relapsed/refractory aggressive B-cell lymphoma. This decision comes as the company explores strategic alternatives, including potential asset sales or a merger.
Promising Early Results Tempered by Safety Concerns
ONCT-808, which targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1), had demonstrated antitumor activity at all dose levels tested in an interim Phase 1 analysis. Notably, a complete metabolic response lasting eight months was observed, and the CAR T-cells persisted long-term. However, one patient treated at the highest dose experienced fatal complications from shock. The patient, an 80-year-old with bulky disease, suffered a grade 5 serious adverse event consistent with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
Pipeline Abandonment and Strategic Shift
Alongside the ONCT-808 study, Oncternal is also discontinuing clinical trials for all other candidates in its pipeline. These include ONCT-534, a dual-action androgen receptor inhibitor for metastatic castration-resistant prostate cancer; zilovertamab, a monoclonal antibody targeting ROR1 in combination with ibrutinib for mantle cell lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma; and ONCT-216, a small-molecule inhibitor of E26 transformation-specific family of oncoproteins for Ewing sarcoma. The company cited available clinical data and capital requirements as driving factors in its decision to end the studies for ONCT-534 and ONCT-808.
Financial Constraints and Future Outlook
In addition to halting all product development activities, Oncternal will reduce its workforce to preserve resources. The company is exploring strategic options, which could include asset sales, licensing, a merger, reverse merger, acquisition, or other business combination.
"The early results during dose escalation in the phase 1/2 studies of ONCT-534 in heavily pretreated patients are disappointing, as the study was supported by extensive preclinical data and was designed to address important unmet medical needs for patients with advanced prostate cancer," said James Breitmeyer, MD, PhD, President and Chief Executive Officer of Oncternal. "In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab, and ONCT-216."
