Ryvu Therapeutics has commenced the Phase II POTAMI-61 clinical trial, marking the dosing of the first patient with RVU120, a novel small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor, for the treatment of myelofibrosis (MF). This study aims to evaluate the safety and efficacy of RVU120 both as a single agent and in combination with ruxolitinib (RUX) in patients with primary or secondary MF.
The POTAMI-61 trial is an open-label, multicenter Phase II study designed to assess key endpoints such as spleen volume reduction (SVR), total symptom score (TSS) improvement, and bone marrow fibrosis reduction. Patients will receive RVU120 until disease progression or withdrawal from the study.
Trial Design and Patient Enrollment
The study is divided into two parts. Part A will enroll approximately 20 patients across two cohorts: one receiving RVU120 as a single agent for those resistant, refractory, or ineligible for JAK inhibitor treatment, and another receiving RVU120 in combination with RUX for patients with a suboptimal response to JAK inhibitors. Depending on the results from Part A, cohorts may be expanded in Part B to further assess the therapy’s anti-tumor activity, tolerability, and safety in a larger cohort of up to 230 patients. There is also a possibility to investigate RVU120 in a frontline setting in cohort 3.
Initially, Part A will enroll patients at clinical sites in Poland and Italy. If the Ryvu Management Board decides to initiate Part B, the study will expand to include additional sites both in the EU and non-EU countries, totaling approximately 50 clinical sites worldwide.
Rationale Behind the Study
The initiation of the POTAMI-61 study is based on RVU120's clinical safety and efficacy data, along with strong preclinical and mechanistic rationale. Preclinical in vivo data have demonstrated the beneficial effects of CDK8 inhibition on improving symptoms such as splenomegaly, hepatomegaly, anemia, and thrombopenia. Notably, RVU120 has shown disease modification properties by reducing mutated allele burden, suggesting its potential as a novel therapeutic strategy in myeloproliferative neoplasms, including MF.
Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics, stated, "We are excited to announce the initiation of the RVU120 Phase II study, POTAMI-61, the fourth Phase II clinical trial included in the RVU120 development plan that Ryvu presented last year. Based on RVU120's effect on bone marrow and hematopoietic cells observed in the RIVER-51 study and translational data generated in myelofibrosis with Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center in New York, we believe there is a strong rationale for RVU120 in the treatment of patients with myelofibrosis, both as a monotherapy and in combination with JAK inhibitors."
RVU120's Broader Development Program
POTAMI-61 is part of RVU120's broader development plan, with other Phase II clinical trials already underway for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). These include the RIVER-52 and RIVER-81 studies in AML and HR-MDS, and the REMARK study in LR-MDS. The data from these trials will contribute to the global RVU120 safety database, supporting potential future regulatory approvals.
