Evelyne Chesné

Immune modulation in solid tumors: a phase 1b study of RO6870810 (BET inhibitor) and atezolizumab (PD-L1 inhibitor)

Daniel Marbach, Jurriaan Brouer-Visser, Laura Brennan, Sabine Wilson et autres

PURPOSE: Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents. PATIENTS AND METHODS: A …

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Immune Modulation in Solid Tumors: A Phase 1b Study of RO6870810 (BET Inhibitor) and Atezolizumab (PD-L1 Inhibitor)

Daniel Marbach, Jurriaan Brouer-Visser, Laura Brennan, Sabine Wilson et autres

ABSTRACT Purpose Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents. Patients and Methods …

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A first-in-human study of the fibroblast activation protein–targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors

Ignacio Melero, Tamara Tanos, Mariana Bustamante, Miguel Fernandez de Sanmamed et autres

This first-in-human study evaluated RO7122290, a bispecific fusion protein carrying a split trimeric 4-1BB (CD137) ligand and a fibroblast activation protein α (FAP) binding site that costimulates T cells for improved tumor cell killing in FAP-expressing tumors. Patients with advanced or metastatic …

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Phase 1b study of the BET protein inhibitor RO6870810 with venetoclax and rituximab in patients with diffuse large B-cell lymphoma

Michael John Dickinson, Javier Briones, Alex Francisco Herrera, Eva M. González-Barca et autres

Bromodomain and extraterminal (BET) proteins are transcriptional activators for multiple oncogenic processes in diffuse large B-cell lymphoma (DLBCL), including MYC, BCL2, E2F, and toll-like receptor signaling. We report results of a phase 1b dose-escalation study of the novel, subcutaneous BET inhibitor RO6870810 …

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A phase 1b dose-escalation/expansion study of BET inhibitor RO6870810 in patients with advanced multiple myeloma

Karthik Ramasamy, Ajay K. Nooka, Hang Quach, Myo Htut et autres

The BRD and extra-terminal (BET) family of proteins have been implicated in malignant transformation and in cancer therapy resistance [ 1 ]. BET inhibition may reduce transcriptional activation of genes important in the biology of multiple myeloma, including MYC, interferon regulatory factor …

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Abstract LB104: Dose-Finding/Expansion Phase Ib Study to Evaluate the Safety and Activity of BET Inhibitor RO6870810 (RO) and Atezolizumab (A) in Patients (pts) with Advanced Ovarian Cancer (OC) or Triple Negative Breast Cancer (TNBC)

Stéphanie Lheureux, Iben Spangaard, Erika Paige Hamilton, George Au‐Yeung et autres

Abstract Background: Transcriptional activation of c-MYC through bromodomain and extra-terminal (BET) proteins contributes to the malignant phenotype of OC and TNBC. RO is a novel thienodiazepine, small molecule, non-covalent inhibitor of the BET family of bromodomains. BET inhibition may also play a …

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A dose escalation study of RO6870810/TEN-10 in patients with acute myeloid leukemia and myelodysplastic syndrome

Gail J. Roboz, Pinkal M. Desai, Sangmin Lee, Ellen Kelly Ritchie et autres

Bromodomain and extra-terminal (BET) proteins can drive carcinogenesis and therapy resistance. RO6870810 (RO) is a novel, small-molecule BET inhibitor. We conducted a study in 32 patients with relapsed/refractory acute myeloid leukemia and hypomethylating agent-refractory myelodysplastic syndrome (NCT02308761). Pharmacodynamic assessments showed decreases in …

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Open Label, Multicenter, Dose-Escalation/ Expansion Phase Ib Study to Evaluate Safety and Activity of BET Inhibitor RO6870810 (RO), Given As Monotherapy to Patients (pts) with Advanced Multiple Myeloma

Karthik Ramasamy, Ajay K. Nooka, Hang Quach, Myo Htut et autres

Introduction Multiple myeloma (MM), relapsed or refractory (R/R) to standard of care therapies, represents a treatment indication with a significant unmet clinical need. Transcriptional activation of c-MYC through bromodomain and extra-terminal (BET) proteins contributes to the malignant phenotype of the disease. RO …

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1025MO First-in-human (FIH) phase I study of RO7122290 (RO), a novel FAP-targeted 4-1BB agonist, administered as single agent and in combination with atezolizumab (ATZ) to patients with advanced solid tumours

Ignacio Melero, Miguel Fernandez de Sanmamed, Emiliano Calvo, Irene Gala Moreno et autres

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BET INHIBITOR RG6146, VENETOCLAX, AND RITUXIMAB IS A HIGHLY ACTIVE REGIMEN IN RELAPSED/REFRACTORY (R/R) DLBCL: INITIAL REPORT OF PHASE 1B SAFETY, BIOMARKER, AND RESPONSE DATA

Michael John Dickinson, J. Briones Mejjide, Alex Francisco Herrera, Eva M. González-Barca et autres

Introduction: Outcomes of patients (pts) with R/R DLBCL are inferior after standard R-CHOP chemotherapy, and a significant proportion of patients has concurrent expression or rearrangements of MYC and BCL2. Bromodomain and extra-terminal (BET) proteins are transcriptional activators for multiple oncogenic processes in …

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Abstract A092: Phase 1 trial of RO6874813, a novel bispecific FAP-DR5 antibody, in patients with solid tumors

Johanna C. Bendell, Jean‐Yves Blay, Philippe Alexandre Cassier, Todd Bauer et autres

Abstract Introduction: FAP-DR5 (RO6874813) is a novel bispecific antibody that binds with high and low affinity to fibroblast activation protein (FAP) and death receptor 5 (DR5), respectively. FAP-driven binding of RO6874813 mediates the high levels of DR5 clustering that are required for …

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A PHASE 1 STUDY OF BET INHIBITION USING RG6146 IN RELAPSED/REFRACTORY (R/R) MYC‐EXPRESSING DIFFUSE LARGE B CELL LYMPHOMA (DLBCL)

Paolo Fabrizio Caimi, Joseph P. Eder, Eric D. Jacobsen, Caron Alyce Jacobson et autres

Methods: CAR T-cell characteristics in axi-cel produced from 62 patients were analyzed by flow cytometry and modeled against CAR T cell levels.In vivo CAR T-cell levels were measured by qPCR.T-cell expansion during production (fold expansion/total days in culture) was compared with CAR …

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