Dr Ged on the Background of the ORCHID Trial in BAP1-Mutated Metastatic RCC

Yasser Mohamed Ali Ged, MBBS, co-director, Kidney Cancer Research Program, assistant professor of oncology, Johns Hopkins Medicine, discusses the background of launching the phase 2 ORCHID trial (NCT03786796) evaluating olaparib (Lynparza) monotherapy in patients with metastatic renal cell carcinoma (RCC) harboring BAP1 or other DNA repair (DDR) gene mutations.

Ged presented interim findings from an interim analysis of patients enrolled (n = 13) in the single-arm trial at the 2023 Kidney Cancer Research Summit. Findings showed that among 11 evaluable patients, olaparib elicited a disease control rate (DCR) of 18%, including an objective response rate of 9% and astable disease rate was 18%. Additionally, 27% of patients experienced tumor reduction, including 2 patients with BAP1-mutated disease. One of those patients experienced a durable partial response, and the other had prolonged stable disease lasting for 10 months.

This phase 2 study is exploring the role of PARP inhibitors in patients with metastatic RCC, Ged begins. Patients enrolled onto the phase 2 study are receiving oral olaparib at 150 mg twice per day for 4 weeks throughout the duration of the safety run-in, followed by olaparib at 300 mg twice per day until disease progression, unacceptable toxicity, or patient withdrawal. Additionally, the primary end point of the study is DCR.

The rationale for this investigation stems from the knowledge that DDR gene alterations are prevalent in multiple cancers, including RCC, Ged explains. Notably, several PARP inhibitors are approved in different indications for other solid tumors for patients who harbor DDR gene alterations, Ged adds.

BAP1 mutations are of particular interest in the RCC space, he expands. This is a tumor suppressor gene that is known to lead to aggressive kidney cancer subtypes and has activity in the DDR pathway, Ged says. Notably, preclinical studies led to the rationale to investigate PARP inhibitors in this subset of patients with metastatic RCC, Ged concludes.