A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420.

Titre officiel

An Open-Label, Multi-Centre, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420 as a Single Agent in Hematologic and Molecular Relapsed/Refractory Acute Myeloid Leukemia

Sommaire:

This open-label, entry-into-human (EIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RO7283420. Escalating doses of RO7283420 will be administered to participants with Acute Myeloid Leukemia (AML) in order to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D).

Description de l'essai

Primary Outcome:

• Percentage of Participants with Adverse Events (AEs)
• Percentage of Participants with Dose-Limiting Toxicities (DLTs)

Secondary Outcome:

• Maximum Reduction (%) from Baseline in Blast Count in Peripheral Blood and/or Bone Marrow
• Percentage of Participants with >= 50% Reduction from Baseline in Blast Count in Peripheral Blood and/or Bone Marrow
• Number of MRD (Measurable Residual Disease) Negative Participants over time According to Local MRD Assessment
• Area Under the Curve (AUC) of RO7283420
• Maximum Concentration (Cmax) of RO7283420
• Minimum Concentration (Cmin) of RO7283420
• Clearance (Cl) of RO7283420
• Volume (V) of RO7283420
• Half-life (T1/2) of RO7283420
• Incidence and Titer of Anti-drug Antibodies (ADA) against RO7283420

The study will include AML participants with measurable disease, for whom standard-of-care (SOC) is not available. Two Groups of AML participants will be included in this study:

• Group I participants will have hematologic relapse/refractory disease (participants not in CR or CRi i.e. with >=5% blast cells in the bone marrow (BM) or presence of circulating blast)

• Group II participants will have molecular relapse/persistent disease (participants with a CR or CRi, and a positive MRD based on local multi-parameter flow cytometry (MFC) assessment). The study consists of three parts:

• Part A (single-participant dose escalation cohorts)

• single participants from Group I will receive increment-based escalating doses until a Grade >=2 AE related to RO7283420 or a clear pharmacodynamic effect

• Part B (multiple-participant dose escalation cohorts)

• multiple-participant cohorts of >=3 participants will be enrolled for dose escalation for Group I and Group II independently.

• Part C (dose expansion)

• participants will receive the respective identified RP2D for that group. Each participant will receive up to 6 cycles of treatment with RO7283420. At the end of cycle 6, only participants achieving at least partial remission may receive three additional treatment cycles.

Voir cet essai sur ClinicalTrials.gov