BP39365 Phase 1b Study of RO6874281 in Metastatic Renal Cell Carcinoma
Research type
Research Study
Full title
AN OPEN-LABEL, MULTI-CENTER, RANDOMIZED, DOSE-ESCALATION, PHASE IB STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND THERAPEUTIC ACTIVITY OF RO6874281 IN COMBINATION WITH ATEZOLIZUMAB + BEVACIZUMAB IN PATIENTS WITH UNRESECTABLE ADVANCED AND/OR METASTATIC RENAL CELL CARCINOMA
IRAS ID
221870
Contact name
Thomas Powles
Contact email
Sponsor organisation
F Hoffmann-La Roche Ltd
Eudract number
2016-003528-22
Duration of Study in the UK
2 years, 3 months, 1 days
Research summary
Metastatic renal cell carcinoma (RCC) is the most lethal urologic cancer and the sixth most common cause of cancer deaths in developed nations. Several agents that target VEGF (bevacizumab) are approved in the treatment of RCC. Additionally, RCC is responsive to immunomodulation (interleukin [IL] 2, anti−programmed death−1 [anti−PD-1], and anti−programmed death−ligand 1 [anti−PD-L1]).
The development of anti-drug antibodies (ADAs) targeting RO6874281 has been observed in the ongoing Phase Ia study, BP29842. ADAs are produced by B cells. Obinutuzumab treatment can be used to reduce the number of B cells, and consequently the number of ADA-producing cells, thereby increasing the likelihood of maintaining efficacious blood exposure of RO6874281 during the course of treatment.
The aim of this study is to evaluate the safety, pharmacokinetic, and therapeutic activity of RO6874281 in combination with atezolizumab ± bevacizumab, following obinutuzumab pre-treatment in patients with unresectable advanced and/or metastatic RCC.
It is expected that 15 DLT evaluable patients will be treated to define the MTD in each arm. For the extension phase of the study, a maximum of 40 response-evaluable patients will be treated in each arm. The initial total sample size for this study is 110 patients.The study consists of a dose-escalation part lasting up to 8 months, and an extension part lasting up to 24 months. Patients will be randomized prior to obinutuzumab pre-treatment to either Arm A or Arm B. In Arm A, patients will receive RO6874281 in combination with atezolizumab. In Arm B, patients will receive RO6874281 in combination with atezolizumab and bevacizumab.
Patients may continue study treatment for a maximum of 24 months.
In the UK it is expected that 7 patients will be enrolled at 1 study centre.
The study is sponsored by F. Hoffman-La Roche Ltd.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
17/WM/0077
Date of REC Opinion
22 Mar 2017
REC opinion
Further Information Favourable Opinion