RIVER-81

CLINICAL STUDY

RIVER-81

A Multicenter, Open-Label, Dose-Finding Clinical Trial to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Efficacy of RVU120 in Combination With Venetoclax in Participants With Acute Myeloid Leukemia Who Failed Prior Therapy With Ventoclax and a Hypomethylating Agent.
TREATMENT
RVU120 and venetoclax in AML
STUDY OVERVIEW
RVU120 exhibits strong synergistic activity when paired with the BCL2 inhibitor venetoclax.

Mechanism of action involves increased expression of proapoptotic proteins like BAD and reduced expression of antiapoptotic proteins like MCL1 and BCL-XL, which counteract cell death signals.

RVU120 and venetoclax work together synergistically across various AML subgroups, even in chemoresistant stem cells, which often trigger relapse in patients. These findings provide a strong rationale for clinical development of the RVU120-venetoclax combination, including patients who have not responded to previous venetoclax treatment.

Study is supported in part by a PLN 62 milion (EUR13.3M) grant from the Polish Medical Research Agency (MRA).

More details on the completed Phase I/II clinical study in AML can be found at ClinicalTrials.gov under NCT06191263
MILESTONE
Updated Phase II data in 2Q25

Explore your eligibility for the RIVER-81 clinical trial

Study population

Women and man 18 Years and older.

Study desig

In Part 1 dose-escalation participants will receive escalating oral doses of RVU120 starting at 125 mg administered every other day on days 1-13, and escalating oral doses of venetoclax starting with 200 mg administered daily on days 1-14 of each 21-day cycle of treatment. The recommended doses for further study will be based on the observed safety, tolerance, PK and PD.

In Part 2, it will be assessed whether the recommended dose level from Part 1 reaches the targetted response criteria, and if reached, Part 3 will be initiated to evaluate further the efficacy and safety of the recommended doses in a larger population.

Inclusion Criteria

Patients must have a diagnosis of AML (per 2022 WHO classification)
Patients must have relapsed or refractory AML (per ELN 2022 criteria)
Patients must have failed first-line treatment with venetoclax combined with a hypomethylating agent
Patients must have no alternative therapeutic options likely to produce clinical benefit
Patients must have ECOG performance status of 0 to 2
Patients must have adequate end organ function defined as:
- WBC < 25 x 10(9)/L on Day 1 prior to first dose of study drug
- Platelet count > 10,000/mcL on Day 1 prior to first dose of study drug
- AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)
- Total bilirubin ≤ 3 x ULN
- Creatinine clearance (Cockcroft & Gault formula) ≥ 50 mL/min
- LVEF (left ventricular ejection fraction) ≥ 40% by electrocardiography
  - Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures

Exclusion Criteria

APL (acute promyelocytic leukemia), the M3 subtype of AML
Active CNS (central nervous system) leukemia
Previous treatment with CDK8 and/or CDK19-targeted therapy
Major surgery within 28 days prior to the first dose of study drug
Hematopoietic stem cell transplant within 120 days prior to the first dose of study drug
Currently pregnant or breast-feeding. Females of child bearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study drug
Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates. This includes but is not limited to:
- Active, Grade ≥2 acute GVHD (graft versus host disease) or requirement for systemic immunosuppressive medication for GVHD
- Evidence of ongoing or uncontrolled systemic bacterial, fungal or viral infection and acute inflammatory conditions (including pancreatitis)
- Ongoing significant liver disease such as cirrhosis, drug-induced liver injury, active hepatitis, or chronic persistent hepatitis B and/or hepatitis C
- Ongoing drug-induced pneumonitis
- Significant cardiac dysfunction, defined as myocardial infarction within 12 months prior to the first dose of study drug, NYHA (New York Heart Association) Class III or IV heart failure, uncontrolled dysrhythmias, poorly controlled angina
- History of ventricular arrhythmia or QTc ≥ 470 ms (Bazett’s formula)
- Prior history of malignancies other than AML, unless disease-free for 5 years or more or prior basal cell carcinoma of the skin, non-metastatic squamous cell carcinoma of the skin, carcinoma in situ of cervix, breast or bladder, and incidental histological finding of prostate cancer (TMN stage T1a or T1b)
  - Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RVU120 and/or venetoclax
  - Taking any medications, herbal supplements, or other substances (including smoking that are known to be strong inhibitors or moderate/strong inducers or sensitive substrates of CYP1A2
  - Taking any medications, over-the-counter medications, foods or herbal supplements that are known to be strong or moderate inhibitors of CYP3A4 or P-gp (P-glycoprotein)
  - Known allergy or hypersensitivity to any component of RVU120 or venetoclax formulations

Participation criteria are verified by the investigator. Participation in the study is contingent upon meeting all inclusion criteria and meeting none of the exclusion criteria. The criteria provided may not be a complete list.

Contact

FOR MEDICAL PROFFESIONALS & INVESTIGATORS

If you are a medical professional, an investigator for a RYVU trial, or would like information about becoming an investigator, please contact us at [email protected] or use contact form.