Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dasatinib | Drug | Dasatinib | ALIAS |
| Dexamethasone | Drug | Dexamethasone | ALIAS |
| Diphenhydramine | Drug | — | UNRESOLVED |
| Paracetamol/acetaminophen | Drug | — | UNRESOLVED |
| RO7283420 | Drug | — | UNRESOLVED |
| Tocilizumab | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Part A: Single Participant Dose Escalation
- description
- Participants from Group I will receive escalating doses of RO7283420, once every 3 weeks (Q3W) starting on Cycle 1, Day 1 (C1D1) for up to 6 cycles with a starting dose of 0.15mg.
- interventionNames
- Drug: RO7283420
- Drug: Tocilizumab
- Drug: Dasatinib
- Drug: Dexamethasone
- Drug: Paracetamol/acetaminophen
- Drug: Diphenhydramine
- type
- EXPERIMENTAL
- label
- Part B: Multiple Participant Dose Escalation
- description
- Multiple-participant cohorts of \>= 3 participants will be enrolled for dose escalation for Group I and Group II independently. Participants will be administered a starting dose of 0.15 mg or highest dose administered in Part A. 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 to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Additionally, step-up dosing regimens with more frequent administrations of RO7283420 during cycle 1 will be evaluated.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * With confirmed diagnosis of primary or secondary AML according to WHO classification 2016, with measurable disease. Eligible participants need to have received standard-of-care (SOC) and have no other SOC options available Participants who are not willing to receive SOC will be not eligible. Two groups of participants (Group I - hematologic relapsed/refractory and Group II - molecular relapsed/refractory) will be included * Participants who have received hematopoietic stem cell transplant (HSCT) must have the HSCT performed ≥ 90 days prior to the first dose of RO7283420 on Cycle 1 Day 1, having demonstrated hematological engraftment and do not have an active Graft versus Host Disease, not requiring immunosuppressive treatment (including but not limited to cyclosporine, tacrolimus, sirolimus, and mycophenolate), which must be stopped at least 28 days prior to the first dose of RO7283420 on Cycle 1 Day 1 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Peripheral blast counts =\< 20,000/mm3 on Cycle 1 Day 1 prior to the first dosing * Confirmed genotype of HLA-A\*02 * Adequate renal (a creatinine clearance of \>=50 mL/min as calculated according to the Cockroft-Gault formula) and adequate liver test results * Male or female participants agree to use contraception and the abstinence requirements to prevent exposure of an embryo to the study treatment Exclusion Criteria: * Acute promyelocytic leukemia (APL) * Core Binding Factor (CBF)-AML Note: participants with r/r CBF-AML after at least 2 salvage attempts can be enrolled into the study * Group II only: participants with normal karyotype and a favorable molecular profile according to ELN guideline 2017 * Participants with active bacterial, fungal or viral infection considered by the Investigator to be clinically uncontrolled or of unacceptable risk upon the induction of neutropenia (i.e. participants who are or should be on antimicrobial agents for the treatment of active infection) * Grade \>= 2 glomerular proteinuria at screening or on Cycle 1 Day 1 prior to the first dosing. * Another primary malignancy (other than AML) that requires active therapy. Adjuvant hormonal therapy is allowed * Clinical evidence or history of central nervous system (CNS) leukemia * Presence of extramedullary disease at screening * Current or past history of CNS disease, such as stroke, CNS inflammation, epilepsy, CNS vasculitis, or neurodegenerative disease * Participants who have a history of clinically significant liver disease, including liver cirrhosis (e.g. Child-Pugh class B and C) or participants who have a history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection * Participants who might refuse to receive blood products and/or have known hypersensitivity to any of the components of RO7283420, tocilizumab, or dasatinib
References
Publications (2)
- DERIVEDHutchings M, Korfi K, Montesinos P, Santoro A, Hou HA, Martinez-Sanchez P, Vives S, Galimberti S, Chen TY, Frigeni M, Garciaz S, Salamero Garcia O, Yeh SP, Yee K, Esteve J, Bajel A, Fleming S, Bretz AC, Attig J, Sun M, Nassiri S, Rutishauser T, Klein C, Ma YM, Schnetzler G, Vauleon S, Yu H, Barata T, Richard M, Simon S, Hinton H, Keshelava N, Subklewe M. Dose escalation study of the HLA-A2-WT1 CD3 bispecific antibody RO7283420 in relapsed/refractory acute myeloid leukemia. Blood Neoplasia. 2025 May 11;2(3):100110. doi: 10.1016/j.bneo.2025.100110. eCollection 2025 Aug. PMID 40746940
- DERIVEDAugsberger C, Hanel G, Xu W, Pulko V, Hanisch LJ, Augustin A, Challier J, Hunt K, Vick B, Rovatti PE, Krupka C, Rothe M, Schonle A, Sam J, Lezan E, Ducret A, Ortiz-Franyuti D, Walz AC, Benz J, Bujotzek A, Lichtenegger FS, Gassner C, Carpy A, Lyamichev V, Patel J, Konstandin N, Tunger A, Schmitz M, von Bergwelt-Baildon M, Spiekermann K, Vago L, Jeremias I, Marrer-Berger E, Umana P, Klein C, Subklewe M. Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC-specific T-cell bispecific antibody. Blood. 2021 Dec 23;138(25):2655-2669. doi: 10.1182/blood.2020010477. PMID 34280257