S227928 + Venetoclax for Leukemia

No longer recruiting at 15 trial locations

Overseen By Institut de Recherches Internationales Servier (I.R.I.S.) Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Servier Bio-Innovation LLC

Must not be taking: QT prolonging drugs

Disqualifiers: Pregnancy, MPNs, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, S227928 (an experimental treatment), both alone and with venetoclax, to determine its safety and effectiveness for certain types of leukemia. The goal is to identify the optimal dose and evaluate the combination's efficacy against the disease. Suitable candidates for this trial include individuals with AML, MDS/AML, or CMML who have experienced a recurrence or lack of improvement after other treatments. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial requires stopping certain medications, especially those that strongly affect specific liver enzymes (CYP3A4 and CYP2C8) and other specific drug interactions. You may need to stop these medications 7 to 14 days before starting the trial and during the trial. It's best to discuss your current medications with the trial team to see if any need to be adjusted.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that S227928, alone or with venetoclax, is under evaluation for safety and effectiveness against certain blood cancers. S227928 is a new drug targeting cancer cells. Studies indicate it works well with venetoclax, a drug already used for some blood cancers. Early tests showed it can shrink tumors in lab models, but it is still under study in humans to assess tolerance and potential side effects.

As this trial is in the early stages, researchers closely monitor for any side effects. The drug is still being tested to determine the safest dose for people. Currently, there is no clear data on how people react to S227928 or its combination with venetoclax. However, venetoclax is already approved for other uses, suggesting it is generally well-tolerated. Participants should expect regular check-ins to monitor their health and any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for leukemia focus on chemotherapy or targeted therapies that interrupt cancer cell growth. However, the investigational drug S227928 is unique because it targets a different pathway, potentially offering a new approach to fighting leukemia. Researchers are excited about S227928, especially in combination with venetoclax, as it may enhance the treatment's effectiveness by targeting cancer cells more precisely and potentially reducing side effects. Additionally, S227928's novel mechanism of action could provide new hope for patients who haven't responded well to existing therapies. Overall, these features make S227928 a promising candidate in the fight against leukemia.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research shows that combining S227928 and venetoclax may effectively treat leukemia. In this trial, some participants will receive S227928 alone, while others will receive the combination of S227928 and venetoclax. Early tests showed that this combination reduced tumor size and extended patient survival. S227928 targets a protein called MCL-1, which aids leukemia cell survival, while venetoclax blocks another protein, BCL-2, which also supports these cells. Together, they appear to attack leukemia cells more effectively. Initial studies in leukemia models have shown promising results, suggesting potential benefits for patients. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain types of blood cancers like AML, MDS/AML, or CMML who have already tried at least one standard treatment and it didn't work (relapsed/refractory). They should be in a decent physical state (ECOG ≤ 2), able to follow strict birth control guidelines if they can have children, and not eligible for more standard treatments. Their blood counts and liver/kidney functions need to meet specific levels.

Inclusion Criteria

My white blood cell count is below 10 x 109/L.

I cannot receive any more standard treatments.

I have taken treatments like erythropoietin or luspatercept for MDS, but not cancer therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 Dose Escalation study to determine the recommended Phase 2 dose (RP2D) of S227928 as a single agent and in combination with venetoclax

Varies

Study visits every two weeks, with additional visits during the first and second cycle

Dose Expansion

Phase 2 Dose Expansion study to assess the efficacy of the selected RP2D of S227928 in combination with venetoclax

Varies

Study visits every two weeks

Follow-up

Participants are monitored for survival every 12 weeks for the next 6 months after the end of treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• S227928
• Venetoclax

Trial Overview The study tests S227928 alone and combined with Venetoclax to see how safe they are, how well they work against leukemia, and what the best dose might be. It starts by finding the right dose (Phase 1) then checks its effectiveness (Phase 2). Participants will visit every two weeks for various health checks including bone marrow tests.

How Is the Trial Designed?

Group I: Dose Expansion - Cohort 2 Experimental Treatment 2 Interventions

For participants with CMML. S227928 in combination with venetoclax at RP2D

Group II: Dose Expansion - Cohort 1 Experimental Treatment 2 Interventions

For participants with R/R AML and MDS/AML. S227928 in combination with venetoclax at RP2D

Group III: Dose Escalation - Arm B Experimental Treatment 2 Interventions

S227928 in combination with venetoclax

Group IV: Dose Escalation - Arm A Experimental Treatment 1 Intervention

S227928 as a single agent

Who Is Running the Clinical Trial?

Servier Bio-Innovation LLC

Lead Sponsor

Trials

9

Recruited

670+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06563804

NCT06563804 | A Study to Evaluate S227928 as a Single ... The objective of this study is to determine the safety, tolerability, and anti-leukemic activity of S227928 as single agent and in combination with ...

2. clinicaltrials.servier.com clinicaltrials.servier.com/trial/NCT06563804/a-study-to-evaluate-s227928-as-a-single-agent-and-in-combination-with-venetoclax-in-patients-with-rr-aml-mdsaml-or-cmml

A Study to Evaluate S227928 as a Single Agent and ... This study is needed to test a new drug called S227928 alone or in combination with venetoclax in participants with the following types of blood disorders:.

3. serviermedical.us serviermedical.us/materials/Maragno_ASH%202024_po_3116.pdf

S227928: A Novel Anti-CD74 ADC with MCL-1 Inhibitor ... The combination of MCL-1 and BCL-2 inhibition has shown promising responses in preclinical models of AML leading to tumor regression and prolonged survival.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-of-s227928-alone-and-with-venetoclax-for-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-myelodysplastic-syndrome-or-chronic-myelomonocytic-leukemia/

Study of S227928 Alone and with Venetoclax for Patients ... The study aims to understand the safety and effectiveness of this combination therapy. Investigated Diseases: Acute Myeloid Leukemia (AML) – A ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124068940

CD74 Antibody Conjugated to an MCL1 Inhibitor (S227928 ... In this study, we highlight the activity of S227928 in combination with venetoclax in models of AML. Aims: To assess the pre-clinical efficacy ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06563804/a-study-to-evaluate-s227928-as-a-single-agent-and-in-combination-with-venetoclax-in-patients-with-r-r-aml-mdsaml-or-cmml

A Study to Evaluate S227928 as a Single Agent and ... The objective of this study is to determine the safety, tolerability, and anti-leukemic activity of S227928 as single agent and in ...

7. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper210048.html

S227928: A Novel Anti-CD74 ADC with MCL-1 Inhibitor ... MCL-1 inhibition has shown promising responses in preclinical models of AML in combination with BCL-2 inhibitors leading to tumor regression and ...