Safety and Efficacy of RVU120 Combined With Venetoclax for Treatment of Relapsed/Refractory AML

ConditionAcute Myeloid Leukemia

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorRyvu Therapeutics SA

About this trial

The goal of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of RVU120 when administered in combination with venetoclax to adult patients with acute myeloid leukemia (AML) who are relapsed or refractory to prior therapy with venetoclax and a hypomethylating agent. The study consists of three parts. Part 1 aims to identify the doses of RVU120 and venetoclax that are considered to be safe and tolerated. Part 2 will assess the safety and efficacy of the doses selected. And Part 3 is a confirmatory cohort where patients will be treated at the same doses assessed in Part 2

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

RVU120
Drug
RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19
Venetoclax
Drug
Venetoclax specifically binds to BCL-2, displacing proapoptotic proteins and triggering events that lead to apoptosis

Treatment groups

98 Participants

are divided into 1 treatment group

Group A: RVU120 + VenetoclaxExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

(Part 1) recommended doses of RVU120 and venetoclax for further study

Incidence and severity of toxicities and number of dose limiting toxicities per dose cohort

Time frame

approx. 12 months

(Parts 2 & 3) CR/CRh rate (Complete Remission/Complete Remission with incomplete Hematologic Recovery)

Preliminary efficacy of RVU120 combined with venetoclax to recommended doses from Part 1. A response of CRh is defined as bone marrow with \<5% blasts, peripheral blood neutrophil count \>0.5 x 10(3)/mcL, and peripheral blood platelet count of \>0.5 x 10(5)/mcL

Time frame

approx. 36 months

Secondary outcomes

Incidence and severity of adverse events (safety and tolerability)

Number and grade of adverse events assessed by CTCAE v5.0

Time frame

approx. 36 months

Duration of response

Time from randomization to disease progression or death in patients who achieve CR/CRh

Time frame

approx. 36 months

Post baseline transfusion independence rate

Transfusion independence is defined as a period of 56 days with no transfusion between the first dose of study drug and the last dose of study drug + 30 days. The rate of conversion of red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependent

Time frame

approx. 36 months

Progression-free survival

Time from randomization until first evidence of disease progression or death

Time frame

approx. 36 months