NCT04580121

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

An Open-Label, Multi-Center, 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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 59 (actual)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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 defined as participants not in complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). * 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) or molecular 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. The treatment period for each participant will be up to 7 months with a maximum number of cycles depending on the dosing frequency the participant receives. Each participant will receive up to 6, 9, and 18 cycles of treatment with RO7283420, when treated with Q3W, every-2-weeks (Q2W), or once-a-week (QW) dosing regimens, respectively. Additional 3, 5, or 9 cycles may be administered for the Q3W, Q2W, and QW dosing regimens, respectively, in case the participants have achieved at least partial remission (PR).

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	RO7283420	RO7283420 will be administered to participants by intravenous (IV) infusion Q3W at a starting dose of 0.15mg. Starting dose levels (double step-up regimen, Q3W) for SC injections was the same as the highest dose levels that have been cleared in the IV double step-up cohorts at that timepoint. Each participant will receive up to 6, 9, and 18 cycles of treatment with RO7283420, when treated with Q3W, Q2W, or QW dosing regimens, respectively.
DRUG	RO7283420	RO7283420 at RP2D will be administered by IV infusion or SC injection as per dosing schedule determined in Part B.
DRUG	Tocilizumab	Tocilizumab will be administered as an IV infusion 8 mg/kg (for participants with a weight of 30 kg and above) and 12 mg/kg (for participants with a weight of less than 30 kg). Tocilizumab will be given as rescue medication.
DRUG	Dasatinib	Dasatinib 100 mg film-coated tablets will be administered daily until symptom resolution (up to 100 mg twice daily \[BID\] for a maximum 3 days); orally. Dasatinib will be given as rescue medication.
DRUG	Dexamethasone	20 mg IV of dexamethasone will be administered as pre-medication at least 60 minutes prior to the all RO7283420 infusions or injections during cycle 1.
DRUG	Paracetamol/acetaminophen	500 or 1000 mg of paracetamol/acetaminophen will be administered orally or by IV as pre-medication at least 30 minutes prior to each RO7283420 infusion or injection.
DRUG	Diphenhydramine	25 mg or 50 mg of diphenhydramine will be administered orally or by IV as pre-medication at least 30 minutes prior to each RO7283420 infusion or injection.

Timeline

• Start date: 2020-11-04
• Primary completion: 2023-08-09
• Completion: 2023-08-09
• First posted: 2020-10-08
• Last updated: 2024-06-03

Locations

23 sites across 10 countries: United States, Australia, Canada, Denmark, France, Germany, Italy, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study