RG6007 / Roche - LARVOL DELTA

BIOMARKER RESULTS OF THE PHASE 1 DOSE ESCALATION TRIAL OF THE HLA-A2-WT1 CD3 T-CELL BISPECIFIC (TCB) ANTIBODY RO7283420 (RG6007) IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (R/R AML) (EHA 2024) - P1 | "In this study we demonstrated the MoA of RO7283420 in R/R AML through key PD effects associated with T-cell activation and expansion in line with known TCB MoAs. Moreover, the association between TIGIT+ T-cellabundance at baseline and blast reduction potentially implies an immunosuppressive microenvironment orexhausted and functionally impaired T cells as extrinsic resistance mechanisms to TCBs in R/R AML,highlighting the need for combinational therapies. Overall, despite the promising PD/biomarker data and asafety profile in line with other TCBs and R/R AML, the study was discontinued due to limited clinical efficacy."

Biomarker • Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Nephrology • Oncology • Solid Tumor • Wilms Tumor • B3GAT1 • CD8 • TIGIT • WT1

A novel tri-specific T cell engager targeting the intracellular oncoprotein WT1 (AACR 2024) - "Safety assessment including cytokine release assay (CRA) and preliminary CMC developability was also performed. WT1-TOPAbody exhibited superior binding affinity to the WT1/HLA-A02 complex while displaying lower binding to off-target peptides and CD34+ HSC from healthy donor than clinical benchmark WT1-CD3 bispecific antibody, RG-6007... WT1-TOPAbody is a differentiated WT1/HLA-A02 targeted T cell engagers that displayed potent and durable anti-tumor activity. These results collectively support the potential of WT1-TOPAbody as a novel therapeutic agent against WT1/HLA-A02+ cancers and warrant its further development."

IO biomarker • Trispecific • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Wilms Tumor • CD34 • CD3E • HLA-A • IL6 • WT1

WP42004: A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420. (clinicaltrials.gov) - P1 | N=59 | Completed | Sponsor: Hoffmann-La Roche | Recruiting ➔ Completed | N=220 ➔ 59 | Trial completion date: Feb 2026 ➔ Aug 2023 | Trial primary completion date: Feb 2026 ➔ Aug 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HLA-A

Dose Escalation of HLA-A2-WT1 CD3 T-Cell Bispecific Antibody in a Phase I Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) (ASH 2023) - P1 | "RO7283420 is the first TCR-L TCB antibody evaluated in AML. We observed pharmacodynamic evidence of T-cell activation and expansion in the clinic, in line with the expected MoA of TCBs, however, at the explored doses, no clear exposure-response relationship and only a modest clinical activity were observed. The safety profile was shown to be consistent with the other TCBs and R/R AML population."

Clinical • P1 data • Acute Myelogenous Leukemia • Dental Disorders • Diabetes • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myositis • Nephrology • Neutropenia • Oncology • Pneumonia • Rare Diseases • Respiratory Diseases • Septic Shock • Solid Tumor • Stomatitis • Thrombocytopenia • Wilms Tumor • ASXL1 • CD8 • FLT3 • HLA-A • NPM1 • RUNX1 • TP53 • WT1

A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420. (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Hoffmann-La Roche | Suspended ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HLA-A

A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420. (clinicaltrials.gov) - P1 | N=220 | Suspended | Sponsor: Hoffmann-La Roche | Recruiting ➔ Suspended

Trial suspension • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HLA-A

A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420. (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2024 ➔ Feb 2026 | Trial primary completion date: Oct 2024 ➔ Feb 2026

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HLA-A

A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420. (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Hoffmann-La Roche | N=160 ➔ 220

Enrollment change • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HLA-A