BP40087 Evaluating RO7122290 in combination with atezolizumab (P1a/b)
Research type
Research Study
Full title
An open-label, multicenter, dose-escalation, phase IA/IB study to evaluate safety, pharmacokinetics, and preliminary anti-tumor activity of RO7122290, a fibroplast activation protein-α (FAP) targeted 4-1BB ligand (CD137L), with or without obinutuzumab pre-treatment, in patients with advanced and/or metastatic solid tumors as single agent or in combination with atezolizumab followed by tumor specific expansion cohort(s)
IRAS ID
1003198
Contact name
Peter Schmid
Contact email
Eudract number
2017-003961-83
Research summary
Cancer immunotherapy (CIT) with immune checkpoint inhibiting (CPI) monoclonal
antibodies has changed the treatment landscape in many cancer types, but 60-80% of
patients with metastatic disease do not derive long-term benefit from this type of CIT.
RO7122290 is expressed on a variety of cells of the immune system, particularly on
CD8+ T and NK cells.
To date, 4-1BB (CD137) agonist monoclonal antibodies have entered clinical
development but demonstrated limited clinical activity as single agent. Objective
responses (OR) have been observed in limited tumor types such as malignant melanoma
and non-Hodgkin’s lymphoma.
Fibroblast activation protein (FAP) is a dimeric Type II transmembrane glycoprotein
with proteolytic activity identified as a promising target for tumor treatment. FAP is
found on cancer-associated stroma cells in >90% of human epithelial malignancies,
particularly on the cell surface of tumor stromal fibroblasts and activated cancerassociated
fibroblasts and pericytes.
In situations where a functional anti-tumor immune response is absent, RO7122290
likely requires combination with a partner that results in activation of T-cells or NK
cells.
The combination with CPIs represents an attractive opportunity as the mechanism of
action is non-overlapping with RO7122290.
The development of anti-drug antibodies (ADAs) is thought mainly mediated by the
stimulation of B-cells, leading to antibody-producing plasma cells.
Obinutuzumab pre-treatment effectiveness was confirmed in various studies where
pretreated patients did not develop ADA
responses.
60 patients will be recruited globally with approximately 8 patients recruited at 3 UK
sites. The study will last approximately 1.5 - 2 years from first patient screened to last
patient last visit.
The study is sponsored by F. Hoffman La Roche
Research Summary; Version Number 4 dated February 2020REC name
HSC REC B
REC reference
20/NI/0091
Date of REC Opinion
12 Aug 2020
REC opinion
Further Information Favourable Opinion