Rebecsinib for Acute Myeloid Leukemia and Myelofibrosis

Overseen By Karla Mack

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Aspera Biomedicines, Inc.

Must not be taking: CYP3A4 drugs

Disqualifiers: Pregnancy, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, rebecsinib, to determine the safest and most effective dose for treating certain blood cancers. It targets individuals with a specific type of Acute Myeloid Leukemia (AML) that hasn't responded to other treatments or has recurred, and those with a high-risk form of Myelofibrosis, a bone marrow disorder. Participants receive the drug on several set days within a month, repeated for six months. Suitable candidates have experienced a relapse or resistance to existing treatments and have not undergone a bone marrow transplant. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any medications that affect certain liver enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2B6) or liver transporters, or are metabolized by these enzymes, at least 5 half-lives before starting the study. If you are on such medications, you may need to stop them or adjust the dose, so it's important to discuss this with the study team.

Is there any evidence suggesting that rebecsinib is likely to be safe for humans?

Research has shown that rebecsinib might be a promising treatment for certain blood cancers. In earlier studies, rebecsinib blocked a specific protein that cancer cells need to grow. These studies also suggested that rebecsinib could be beneficial while being fairly well-tolerated at certain doses.

However, most of this information comes from pre-clinical research, conducted before testing on people. The trial under consideration is in an early phase, primarily focused on finding the safest dose for humans. While early results are encouraging, researchers are still learning about rebecsinib's safety in people. Participants in the trial will help researchers determine how safe and effective rebecsinib truly is. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Rebecsinib is unique because it targets specific genetic mutations often found in acute myeloid leukemia (AML) and myelofibrosis, which are not addressed by standard treatments like chemotherapy or targeted therapies such as FLT3 inhibitors. Unlike traditional treatments, which can affect both healthy and cancerous cells, rebecsinib is designed to minimize damage to normal cells by honing in on these mutations. Researchers are excited because this precision approach could lead to more effective treatment outcomes with potentially fewer side effects, offering hope for patients with these challenging conditions.

What evidence suggests that rebecsinib might be an effective treatment for acute myeloid leukemia and myelofibrosis?

Research has shown that rebecsinib is a promising new treatment for certain blood cancers. It blocks a protein called ADAR1, which aids cancer growth. Studies indicate that rebecsinib can stop and even reverse the harmful effects of this protein in cancer cells. This is crucial for conditions like Secondary Acute Myeloid Leukemia (sAML) and Myelofibrosis (MF), where traditional treatments might not be effective. Early lab studies found that rebecsinib can reduce the survival of harmful cancer cells in these diseases. While more research is needed, these findings suggest rebecsinib could be a powerful new option for treating these challenging conditions. ^{1 2 5 6 7}

Who Is on the Research Team?

James Mangan, MD, PhD

Principal Investigator

UC San Diego Moores Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Secondary Acute Myeloid Leukemia that's come back or hasn't responded to treatment, or high-risk Myelofibrosis. Participants need good kidney function, acceptable blood counts and liver enzymes, and can't be pregnant. They must not be eligible for bone marrow transplant and should have recovered from previous treatments.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent

Calculated Creatinine clearance (CrCl) > 60 mL/min

At relapse, must have ≥5% leukemic bone marrow blasts

Exclusion Criteria

Pregnant or breast feeding females

Currently receiving another investigational agent

A QTc >470 msec on ECG

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rebecsinib infusion on Day 1, Day 4, Day 8, and Day 11 of each 28-day cycle for a total of 6 cycles

24 weeks

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Rebecsinib

Trial Overview The study tests the safety and effectiveness of a new drug called rebecsinib in patients with sAML or high-risk MF. It involves receiving rebecsinib infusions on specific days over six 28-day cycles to determine the best dose.

Who Is Running the Clinical Trial?

Aspera Biomedicines, Inc.

Lead Sponsor

Tempus AI

Industry Sponsor

Trials

18

Recruited

20,700+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07250646?aggFilters=status%3A

A Study of Rebecsinib for Patients With Relapsed ... Study outcomes will be measured by adverse event data, response rates, progression free survival and overall survival. Pharmacodynamics and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10134781/

Reversal of Malignant ADAR1 Splice Isoform Switching with ... As a potent first-in-class ADAR1 inhibitor, Rebecsinib decreases RNA editing by inhibiting ADAR1 splicing into the most active editase, ADAR1p150.

3. health.ucsd.edu health.ucsd.edu/news/press-releases/2023-02-16-small-molecule-drug-reverses-adar1-induced-cancer-stem-cell-cloning-capacity/

Small Molecule Drug Reverses ADAR1-induced Cancer Stem ... "In these studies, rebecsinib appears to have great potential for stopping and reversing ADAR1 hyper-editing that leads from non-invasive pre- ...

4. mdpi.com mdpi.com/2075-1729/14/3/309

Recent Advances towards the Understanding of Secondary ... Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD)

5. researchgate.net researchgate.net/figure/Rebecsinib-inhibits-ADAR1p150-mediated-high-risk-MF-HPC-and-LSC-survival-A-Schematic_fig3_368587082

Rebecsinib inhibits ADAR1p150 mediated high-risk MF ... Rebecsinib inhibits ADAR1p150 mediated high-risk MF HPC and LSC survival (A) Schematic diagram of in vitro MF HPC and LSC survival and self-renewal assays.

6. cell.com cell.com/cell-stem-cell/pdf/S1934-5909(23)00008-5.pdf

Reversal of malignant ADAR1 splice isoform switching with ... acute myeloid leukemia (sAML) therapeutic resistance, and (3) ... These data provide evidence for a favorable thera- peutic index with Rebecsinib.

7. mpnresearchfoundation.org mpnresearchfoundation.org/wp-content/uploads/2022/04/2022-Spring-MPNRF-Newsletter.pdf

UPDATE And why is it that only some people with myelofibrosis progress to AML (acute myeloid leukemia)? ... efficacy and safety data. These data are used to ...