Dr Serzan on the Rationale for Evaluating Botensilimab Plus Balstilimab in Advanced RCC

Michael Serzan, MD, medical oncologist, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, discusses the rationale for evaluating botensilimab (AGEN1181) plus balstilimab (AGEN2034) in patients with advanced renal cell carcinoma (RCC) in the phase 2 ARCITECT (NCT05928806) trial.

ARCITECT is a multicenter, investigator-initiated trial evaluating the efficacy and safety of botensilimab with balstilimab vs nivolumab (Opdivo) plus ipilimumab (Yervoy) in this patient population. This trial is grounded in preclinical research that suggests a novel approach to improving the effectiveness of immune checkpoint inhibitors, Serzan begins. Additionally, the study was supported by earlier work from a phase 2 trial (NCT03117309) evaluating nivolumab monotherapy followed by a nivolumab plus ipilimumab boost in non-responding patients with treatment-naive RCC, he explains. Translational findings from this study revealed that the presence of regulatory T cells (Tregs) expressing PD-1 on their surface was associated with poor responses to nivolumab monotherapy. This insight suggested that targeting these Tregs could enhance the effectiveness of PD-1-based therapies, Serzan states.

Botensilimab is an immuno-oncology agent designed to enhance T-cell priming, deplete intratumoral Tregs, and activate myeloid cells by leveraging novel FcyR-associated mechanisms of action. When combined with balstilimab, an anti-PD-1 therapy, this anti-CTLA4 agent has shown promising antitumor activity, particularly in cancers where the combination of nivolumab and ipilimumab has proven ineffective, he continues.

The ARCITECT trial will include patients with favorable, intermediate, or poor risk clear cell RCC who have not received prior adjuvant or neoadjuvant systemic therapy, Serzan reports. Patients will be randomly assigned to receive either the botensilimab/balstilimab combination or the standard nivolumab/ipilimumab regimen for up to 2 years. Stratification factors will include IMDC risk groups and the presence of sarcomatoid histology. The primary end point of the trial is the overall response rate as measured by RECIST 1.1 criteria, he notes. This study aims to determine whether the novel combination of botensilimab and balstilimab can offer superior outcomes compared to the established nivolumab/ipilimumab regimen, potentially providing a new therapeutic option for patients with clear cell RCC, Serzan concludes.