SELLAS Life Sciences Initiates Pediatric AML Patient Dosing in Phase 2 SLS009 Trial

Analysis reveals significant industry trends and economic implications

Release Date

2025-05-16

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

SELLAS Life Sciences announced the first pediatric patient has been dosed in its ongoing Phase 2 trial of SLS009 (tambiciclib) for relapsed/refractory acute myeloid leukemia (r/r AML). This follows promising data from Cohort 3 and leverages the drug's Rare Pediatric Disease Designation (RPDD). The trial evaluates SLS009's safety, tolerability, and efficacy in combination with venetoclax and azacitidine. Success could lead to a Priority Review Voucher (PRV) upon FDA approval. The trial is designed to identify biomarkers and enrich future trials.

Key Highlights

  • First pediatric AML patient dosed in the Phase 2 trial of SLS009.
  • Trial is evaluating SLS009 in combination with venetoclax and azacitidine.
  • SLS009 has received Rare Pediatric Disease Designation (RPDD).
  • Potential for Priority Review Voucher (PRV) upon FDA approval.

Incidence and Prevalence

Global Incidence of AML:

Global Prevalence of AML:

Important Note: The incidence and prevalence of AML vary based on factors such as age, sex, region, and the specific time period studied. The most recent data suggests a continued rise in the global incidence of AML, particularly among older adults, while age-standardized incidence rates may be stabilizing or even declining in some regions.

Mechanism of Action

Several novel therapeutic approaches are under investigation for acute myeloid leukemia (AML). While many mechanisms of action are being explored, three prominent areas of focus in clinical trials for non-approved AML drugs include:

  1. Menin Inhibitors:

  2. Mechanism: Menin is a protein that interacts with theMLL fusion protein, a common oncogenic driver in AML. Menin inhibitors disrupt this interaction, leading to downregulation of HOX genes and other oncogenes crucial for MLL-rearranged AML survival. These inhibitors show promise in preclinical studies and early clinical trials, particularly for AML with MLL rearrangements or NPM1 mutations.

  3. Examples: KO-539, SNDX-5613
  4. Clinical Trial Status: Several menin inhibitors are currently in clinical trials, showing promising results in terms of response rates and duration of response, especially in combination with other AML therapies.

  5. DOT1L Inhibitors:

  6. Mechanism: DOT1L is a histone methyltransferase specifically responsible for histone H3 lysine 79 methylation (H3K79me). This methylation is crucial for the expression of oncogenes in MLL-rearranged AML. DOT1L inhibitors block this methylation, leading to downregulation of these oncogenes and inducing differentiation and apoptosis of leukemic cells.

  7. Examples: Pinometostat (EPZ-5676)
  8. Clinical Trial Status: DOT1L inhibitors have shown promising results in early-phase clinical trials, particularly in patients with MLL-rearranged AML. However, further studies are needed to confirm their efficacy and optimize their use in combination with other therapies.

  9. Bispecific Antibodies and Immune Therapies:

  10. Mechanism: Bispecific antibodies simultaneously target two different antigens, one on the surface of AML cells and the other on immune effector cells (e.g., T cells or NK cells). This brings the immune cells into close proximity with the AML cells, triggering their destruction. Other immune therapies, such as checkpoint inhibitors and CAR T-cell therapy, aim to enhance the anti-leukemic activity of the immune system.

  11. Examples: Flotetuzumab (CD33/CD3), AMG 330 (CD33/CD3), Magrolimab (CD47), Sabatolimab (TIM-3)
  12. Clinical Trial Status: Several bispecific antibodies and other immune therapies are currently in clinical trials for AML. While some have shown promising early results, challenges remain in terms of optimizing their efficacy and managing immune-related adverse events.

It's important to note that the clinical trial landscape for AML is constantly evolving, and new targets and mechanisms of action are continuously being explored. The three areas mentioned above represent some of the most promising approaches currently under investigation, but other strategies, such as targeting RNA splicing factors, developing novel FLT3 inhibitors, and exploring combination therapies, are also actively being pursued.

Study Design Parameters

Several clinical trials have explored various treatment strategies and novel agents for Acute Myeloid Leukemia (AML). Here's a summary of study design parameters and endpoints in key trials:

Early-Phase Trials:

Phase 3 Trials:

Specific Trial Examples and Design Features:

Key Considerations in AML Trial Design:

This summary highlights the diversity of study designs and endpoints used in AML clinical trials. The specific design and endpoints chosen depend on the research question, patient population, and the stage of drug development.

Drug used in other indications

SLS009 (tambiciclib), a highly selective CDK9 inhibitor, is currently being investigated in clinical trials for various cancer types beyond acute myeloid leukemia (AML). While many trials are still ongoing and results are not yet fully available, the following indications and intervention models are being explored:

Solid Tumors:

Hematologic Malignancies (other than AML):

Intervention Models:

The intervention models used in these trials vary depending on the specific disease and the combination of agents being studied. Common models include:

It is important to note that the information provided here is based on publicly available data and may not be exhaustive. The specific indications and intervention models being investigated for SLS009 may change as research progresses.

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