RVU120 in Patients With Intermediate or High-risk, Primary or Secondary Myelofibrosis (POTAMI-61)

An Open-Label Clinical Trial of RVU120 as Monotherapy and in Combination With Ruxolitinib in Patients With Intermediate or High-Risk, Primary or Secondary Myelofibrosis (POTAMI-61)

The objective of this clinical trial is to evaluate the efficacy (how well the drug works), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the study drug, RVU120, in treating adult patients with intermediate or high-risk, primary or secondary myelofibrosis. RVU120 will be given as a single agent or in combination with ruxolitinib.

Study Overview

• Status: Recruiting
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: RVU120; Drug: Ruxolitinib

Detailed Description

The study schedule consists of a screening period up to 28 days, a 21-day treatment period, an end of treatment visit (30 days) and a 1-year follow-up where participants will be contacted every 3 months for assessment. Study duration for each participant will vary depending on the number of 21-day treatment cycles received. The study is open to participants aged ≥18 years with intermediate or high-risk, primary or secondary MF who have been previously treated, are ineligible for, or had a suboptimal response to JAK inhibitor therapy. Participants must have adequate organ function (kidney, liver) and no history of hematopoietic stem cell transplant. Participants may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Head of Clinical Operations; Phone Number: 48 123140200; Email: clinicaltrials@ryvu.com

Study Locations

• Italy
  • Bologna, Italy
    • Recruiting
    • Policlinico Sant'Orsola-Malpighi
    • Contact: Francesca Palandri, Prof.
    • Principal Investigator: Francesca Palandri, Prof.
  • Brescia, Italy
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
    • Contact: Domenico Russo, Prof.
    • Principal Investigator: Domenico Russo, Prof.
  • Catania, Italy
    • Recruiting
    • Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"
    • Contact: Giuseppe Palumbo, Prof.
    • Principal Investigator: Giuseppe Palumbo, Prof.
  • Meldola, Italy
    • Recruiting
    • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
    • Contact: Alessandro Lucchesi, MD PhD
    • Principal Investigator: Alessandro Lucchesi, MD PhD
  • Milan, Italy
    • Recruiting
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
    • Contact: Barbara Mora, Dr
    • Principal Investigator: Barbara Mora, Dr
• Poland
  • Biała Podlaska, Poland
    • Recruiting
    • Wojewódzki Szpital Specjalistyczny W Białej Podlaskiej
    • Contact: Piotr Centkowski, MD PhD
    • Principal Investigator: Piotr Centkowski, MD PhD
  • Bydgoszcz, Poland
    • Recruiting
    • Szpital Uniwersytecki nr 2 im. dr Jana Biziela
    • Contact: Jarosław Czyż, Prof.
    • Principal Investigator: Jarosław Czyż, Prof.
  • Chorzów, Poland
    • Recruiting
    • M2M Med. Sp. z o.o. Sp. j.
    • Contact: Katarzyna Dulik, MD
    • Principal Investigator: Katarzyna Dulik, MD
  • Gdansk, Poland
    • Recruiting
    • Centrum Wsparcia Badań Klinicznych UCK Ośrodek Badań Klinicznych Wczesnych Faz
    • Contact: Witold Prejzner, MD PhD
    • Principal Investigator: Witold Prejzner, MD PhD
  • Katowice, Poland
    • Recruiting
    • Pratia Hematologia Sp. z o.o.
    • Contact: Sebastian Grosicki, Prof.
    • Principal Investigator: Sebastian Grosicki, Prof.
  • Kielce, Poland
    • Completed
    • Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej
  • Krakow, Poland
    • Recruiting
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
    • Contact: Tomasz Sacha, Prof.
    • Principal Investigator: Tomasz Sacha, Prof.
  • Lublin, Poland
    • Recruiting
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
    • Contact: Aneta Szudy-Szczyrek, MD, PhD habil.
    • Principal Investigator: Aneta Szudy-Szczyrek, MD, PhD habil.
  • Torun, Poland
    • Recruiting
    • Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
    • Contact: Marcin Rymko, MD PhD
    • Principal Investigator: Marcin Rymko, MD PhD
  • Warsaw, Poland
    • Recruiting
    • LUX MED Onkologia Sp. z o.o.
    • Contact: Joanna Barankiewicz, MD PhD
    • Principal Investigator: Joanna Barankiewicz, MD PhD
  • Warsaw, Poland
    • Recruiting
    • Wojskowy Instytut Medyczny Państwowy Instytut Badawczy
    • Contact: Krzysztof Gawroński, MD PhD
    • Principal Investigator: Krzysztof Gawroński, MD PhD
  • Wroclaw, Poland
    • Recruiting
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
    • Contact: Tomasz Wróbel, Prof.
    • Principal Investigator: Tomasz Wróbel, Prof.
  • Zielona Góra, Poland
    • Completed
    • Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years
2. Diagnosis of Primary or Secondary myelofibrosis (MF) according to the revised World Health Organization (WHO) criteria (Arber 2022).
3. Intermediate or high-risk disease.
4. Resistant or refractory to prior Janus kinase (JAK) inhibitor treatment or ineligible for JAK inhibitor treatment in the opinion of the investigator; or Suboptimal response to JAK inhibitor treatment. Note: a suboptimal response to JAK inhibitor treatment is defined as spleen size increase by palpation >25% after the first 3 months of treatment with a JAK inhibitor or persistent splenomegaly (spleen volume of >450 cm3) after at least 6 months of JAK inhibitor treatment and presence of 1 symptom score ≥5 or 2 symptom scores ≥3, new or persistent red blood cell (RBC) transfusion dependence; or may include participants naïve to previous treatment with JAK inhibitor.
5. Measurable splenomegaly as demonstrated by palpable spleen measuring ≥5 cm below the left costal margin. The edge of the spleen should be measured from the mid-clavicular line on the left side of the abdomen to the point of greatest splenic protrusion; or spleen volume of ≥450 cm3 measured by magnetic resonance imaging(MRI) or computed tomography (CT).
6. Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the following symptoms: night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, bone or muscle pain, and inactivity.
7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.

8. Adequate hematologic function defined as:

   1. absolute neutrophil count (ANC) ≥1.0 × 109/L (without growth factor support)
   2. platelet count ≥50 × 109/L (Cohort 2 and Cohort 3 only)
9. Adequate renal function defined as calculated or measured creatinine clearance (CrCl) of ≥30 mL/minute using the formula of Cockcroft and Gault (see Section 15).
10. Adequate liver function defined as (a) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN); (b) alkaline phosphatase (ALP) ≤2 × ULN (ALP ≤5 × ULN for participants with isozymes specific to bone); (c) bilirubin <2 × ULN or bilirubin ≤3 × ULN if due to Gilbert's disease.

Exclusion Criteria:

Each participant must not meet any of the following:

1. Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%.
2. Prior history of hematopoietic stem cell transplant.
3. Participation in any other study in which receipt of an investigational new drug occurred within 4 weeks prior to Cycle 1 Day 1.

4. Active known second malignancy with the exception of any of the following:

   1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
   2. Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥2 years
   3. Low-risk prostate cancer with a Gleason score <7 and a prostate-specific antigen (PSA) level <10 ng/mL
   4. Any other cancer from which the participant has been disease-free for ≥3 years.
5. Known or suspected allergy to RVU120 or RUX.
6. Impairment of gastrointestinal function or gastrointestinal disease
7. Major surgical procedure or significant traumatic injury within 28 days Placement of a vascular access device or minor surgery is permitted within 14 days before Cycle 1 Day 1 (provided that the wound has healed).
8. Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed.
9. Significant cardiac dysfunction defined as myocardial infarction within 12 months of Cycle 1 Day 1, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled dysrhythmias, poorly controlled angina (Section 17), or left ventricular ejection fraction (LVEF) <40% as per echocardiography or multiple gated acquisition (MUGA) scan.
10. 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, within less than 5 half-lives prior to Cycle 1 Day 1.
11. History of ventricular arrhythmia, or QTc ≥470 millisecond (Bazett's formula).
12. Known active human immunodeficiency virus (HIV) infection
13. Current active liver disease from any cause
14. Pregnant or lactating females.
15. Any other prior or current medical or psychiatric condition, intercurrent illness, surgical history, physical or electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating circumstance (e.g., alcohol or drug addiction) that, in the Investigator's opinion, could jeopardize participant safety or interfere with the objectives of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RVU120; Cohort 1 RVU120 is administered at 250 mg as a single agent every other day on days 1, 3, 5, 7, 9, 11, and 13 of 21-day treatment cycles, or at an adjusted dose, to participants with intermediate or high-risk, primary or secondary MF who have been previously treated with or are ineligible for treatment with a JAK inhibitor.	Drug: RVU120; RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19; Other Names: SEL120
Experimental: RVU120 + ruxolitinib; Cohort 2 RVU120 is administered at 250 mg every other day on days 1, 3, 5, 7, 9, 11, and 13 of 21-day treatment cycles or at an adjusted dose, in combined with ruxolitinib administered orally twice daily following the dosing instructions in current prescribing information, to participants with intermediate or high risk, primary or secondary MF experiencing suboptimal response to JAK inhibitor.	Drug: RVU120; RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19; Other Names: SEL120; Drug: Ruxolitinib; Ruxolitinib is a kinase inhibitor which inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2; Other Names: RUX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the number of participants with a response (anti-cancer activity) to RVU120 when administered as a single agent or in combination with ruxolitinib	The proportion of participants with spleen volume reduction (SVR) of ≥35% after 24 weeks of study treatment evaluated by magnetic resonance imaging (MRI) or computed tomography (CT)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To further evaluate the number of participants having a response (anti-cancer activity and/or clinical benefit) to RVU120 when administered as a single agent or in combination with ruxolitinib	The proportion of participants with ≥1 Grade bone marrow fibrosis improvement after 24 weeks of study treatment	12 months
Duration of spleen response	Assessed as the time from initial SVR of ≥35% by MRI/CT until disease progression or death, whichever occurs first	12 months
Number of participants with leukemic transformation	Assessed as the proportion of participants with bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting 2 weeks	12 months
Number of participants with hematological (clinical) improvement	Assessed as the proportion of participants with hematological (clinical) improvement as defined by International Working Group (IWG) Consensus Criteria (see Tefferi et al., 2006 for further details)	12 months
Progression-Free Survival (PFS)	Assessed as time from the time from first treatment to the first occurrence of disease progression or death	12 months
Overall Survival (OS)	Assessed as time from the time from first treatment to death	12 months
Incidence and severity of adverse events (AEs)	Assessed as the number and grade of adverse events assessed by CTCAE v5.0	12 months
Change in symptom burden	Assessed as the proportion of participants achieving at least a 50% reduction in symptom burden after 24 weeks of commencing study treatment as assessed by the Total Symptom Score (TSS) using the Myelofibrosis Symptom Assessment Form (MFSAF). Each item is rated on a scale from 0 (Absent) to 10 (Worst Imaginable).	Baseline and week 24
Absolute change in TSS from baseline	Assessed as the number of participants with absolute change in Total Symptom Score (TSS) from baseline assessed using the Myelofibrosis Symptom Assessment Form (MFSAF). Each item is rated on a scale from 0 (Absent) to 10 (Worst Imaginable).	Baseline and week 24

Collaborators and Investigators

• Sponsor: Ryvu Therapeutics SA

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: primary; secondary; high-risk; intermediate
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Hematologic Diseases; Neoplastic Processes; Bone Marrow Diseases; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasm Metastasis; Primary Myelofibrosis; ruxolitinib
• Other Study ID Numbers: POTAMI-61

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No