OPN-6602 received FDA fast track designation for relapsed/refractory multiple myeloma after at least 4 prior lines of therapy.
The FDA has granted fast track designation to OPN-6602 as a potential therapeutic option for patients with relapsed/refractory multiple myeloma who received at least 4 prior lines of therapy.1
OPN-6602 is an oral, small molecule EP300 and CREB-binding protein (CBP) inhibitor. Preclinical multiple myeloma models have demonstrated that inhibition of EP300 and CBP leads to cell cycle arrest and apoptosis, supporting the rationale for evaluating the agent in this patient population.2 In a preclinical OPM-2 xenograft model, OPN-6602 monotherapy displayed a 71% tumor growth inhibition (TGI); the addition of dexamethasone led to a TGI greater than 100%, and tumor regressions were observed in animal models with the use of OPN-6602 in combination with dexamethasone and pomalidomide (Pomalyst) or dexamethasone and mezigdomide (CC-92480; TGI >100%).
Notably, dosing was stopped after 13 days to monitor for duration of response, which persisted to day 30 for the combination of OPN-6602, dexamethasone, and pomalidomide, and to day 42 for OPN-6602 plus dexamethasone and mezigdomide.
OPN-6602 is currently being evaluated in a phase 1 trial (NCT06433947) for patients with relapsed/refractory multiple myeloma.1,3
“Opna Bio has been a pioneer in the EP300/CBP inhibitor space, and OPN-6602 was selected for its potency, selectivity, and optimized pharmacokinetic properties. We are encouraged by the progress of the study to date and look forward to reporting emerging clinical data at an upcoming scientific congress,” Reinaldo Diaz, chief executive officer of Opna Bio, stated in a news release.1
The phase 1, multicenter, open-label, dose-escalation and -expansion trial is examining the use of OPN-6602 alone or in combination with dexamethasone.3 Investigators are enrolling patients at least 18 years of age with multiple myeloma who are relapsed/refractory to at least 3 prior lines of therapy that included an immunomodulatory drug, proteosome inhibitor, and anti-CD38 antibody. They cannot be candidates for standard therapies with known clinical benefit, or they need to be intolerant to standard-of-care therapies. Patients are also required to have adequate hematologic, renal, liver, and cardiac function.
The study is excluding patients with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, Waldenström macroglobulinemia, IgM myeloma, or active plasma cell leukemia. Other key exclusion criteria comprise known central nervous system involvement; prior Stevens Johnson syndrome; receipt of localized radiation therapy within 2 weeks of first study dose; autologous stem cell transplant or bone marrow transplant within 90 days of the first study dose; allogeneic stem cell transplant or solid organ transplant within 12 months of first dose of study drug; and poorly controlled Type 2 diabetes.
In the dose-escalation phase, patients are receiving OPN-6602 once daily as monotherapy or in combination with dexamethasone at 40 mg on days 1, 8, and 15 of each cycle. Dose escalation also features a monotherapy cohort.
The study’s primary end points are the incidence and type of dose-limiting toxicities, incidence and type of treatment-emergent adverse effects, and the proportion of patients with clinical laboratory abnormalities.
The trial is currently enrolling patients at 11 sites in the United States, with an estimated target enrollment of 130 patients.
In February 2025, the FDA also
