Ryvu Therapeutics Presents Promising Clinical Data on Romaciclib and Dapolsertib at ASH 2025
核心洞察
Romaciclib (搜索) demonstrates efficacy in restoring venetoclax sensitivity in resistant acute myeloid leukemia patients, achieving 23-43% composite complete remission rates in the Phase II RIVER-81 trial.
The CDK8 (搜索)/CDK19 (搜索) inhibitor shows clinically meaningful spleen volume and symptom reductions in myelofibrosis patients in the post-JAK inhibitor setting through the POTAMI-61 study.
Dapolsertib represents the first clinical evaluation of a dual PIM (搜索)/FLT3 (搜索) kinase inhibitor in aggressive B-cell lymphomas, being tested both as monotherapy and in combination with glofitamab.
Ryvu Therapeutics (搜索) will present compelling clinical data on its lead oncology candidates romaciclib (搜索) (RVU120) and dapolsertib (MEN1703) at the 2025 American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, December 6-10, 2025. The company announced four accepted abstracts showcasing meaningful therapeutic activity across multiple hematologic malignancies.
Romaciclib Shows Promise in Venetoclax-Resistant AML
The Phase II RIVER-81 study evaluating romaciclib (搜索) in combination with venetoclax has enrolled 48 patients with relapsed or refractory acute myeloid leukemia following frontline venetoclax plus hypomethylating agent (VEN+HMA) therapy failure. As of July 11, 2025, the selective CDK8 (搜索)/CDK19 (搜索) inhibitor demonstrated encouraging efficacy signals with composite complete remission (CR + CRi) rates of 23% in Stage 1 of Part 2 and 43% among treated patients in Cohort 4.
"Early efficacy signals suggest romaciclib (搜索) may restore sensitivity to venetoclax in resistant AML," according to the study data. Among 28 evaluable patients, several achieved ongoing durable responses, with five of eight responding patients remaining on therapy for durations ranging from 0.6 to 7 months.
The combination showed favorable tolerability, with no dose-limiting toxicities observed up to romaciclib (搜索) 200 mg daily combined with venetoclax 400 mg daily. Pharmacodynamic assessments demonstrated robust inhibition of STAT5 phosphorylation, confirming on-target CDK8 (搜索)/19 activity. The most common adverse events were low-grade gastrointestinal symptoms, anemia, febrile neutropenia, and pneumonia.
Clinical Activity Demonstrated in Myelofibrosis
The Phase II POTAMI-61 study is evaluating romaciclib (搜索) as monotherapy and in combination with ruxolitinib in patients with myelofibrosis who have failed or shown suboptimal response to JAK inhibitor therapy. As of July 25, 2025, 23 patients were enrolled across both treatment arms.
Among four evaluable patients, one achieved spleen volume reduction ≥20% at 24 weeks, while three showed some degree of spleen volume reduction. Two patients achieved >50% reduction in total symptom score, with one patient demonstrating complete symptom resolution. Notably, one patient showed improvement in bone marrow fibrosis after 12 weeks of treatment.
Treatment was generally well tolerated, with the most common adverse events being grade 1-2 nausea (52%) and vomiting (43%). Pharmacokinetic results confirmed expected exposure and no drug-drug interaction between romaciclib (搜索) and ruxolitinib.
Erythroid Response Observed in Lower-Risk MDS
The Phase II REMARK study is investigating romaciclib (搜索) in patients with lower-risk myelodysplastic neoplasms, a disease characterized by anemia and limited treatment options. As of the data cutoff, 42 patients had initiated treatment, with 15 remaining on therapy.
Preliminary results demonstrated early signs of clinical activity, including one patient with high transfusion burden (≥8 RBC units/16 weeks) who achieved a primary erythroid response per IWG 2018 criteria after 24 weeks of treatment. This responder carried an SF3B1 mutation and had previously failed three standard therapies including erythropoiesis-stimulating agents, luspatercept, and lenalidomide.
First Clinical Evaluation of Dapolsertib in Lymphomas
The Phase II JASPIS-01 study represents the first clinical evaluation of dapolsertib, a dual PIM (搜索)/FLT3 (搜索) kinase inhibitor, in aggressive B-cell lymphomas. The study is evaluating dapolsertib as monotherapy and in combination with the CD20xCD3 bispecific antibody glofitamab in patients with relapsed or refractory disease who have received at least two prior lines of therapy.
Dapolsertib targets key oncogenic and survival pathways, including MYC- and BCL6-associated signaling, and has demonstrated preclinical synergy with anti-CD20 antibodies. The study aims to explore dapolsertib's potential to overcome resistance associated with CD20 downregulation.
As of July 11, 2025, enrollment in Part 1 is ongoing across France, Poland, Spain, and the UK, with additional site activations planned. Two dosing schedules are being explored: 125 mg (2 weeks on/1 week off) and 150 mg (1 week on/2 weeks off) to identify the optimal therapeutic window.
Strong Financial Position Supports Continued Development
Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics (搜索), commented: "We are excited to share the latest data highlighting the breadth and growing maturity of Ryvu's clinical pipeline. Romaciclib (搜索) continues to demonstrate meaningful activity across multiple hematologic malignancies, while dapolsertib offers an innovative approach to address treatment resistance in aggressive lymphomas."
As of November 11, 2025, Ryvu maintained a cash position of €28.2 million, with an additional €18.5 million secured in non-dilutive grant funding. The company has also expanded its strategic collaboration with BioNTech to accelerate site activation and patient enrollment for oncology clinical programs in Poland.
The clinical data presentations at ASH 2025 will provide important insights into Ryvu's pipeline maturation and the potential of these novel targeted therapies to address unmet medical needs in hematologic malignancies.