Dr Ged on Interim Data With Olaparib in DNA Repair Gene–Mutated mRCC

Yasser Mohamed Ali Ged, MBBS, co-director, Kidney Cancer Research Program, and assistant professor of oncology, Johns Hopkins Medicine, discusses the phase 2 ORCHID trial (NCT03786796).

ORCHID is a single-arm trial evaluating olaparib (Lynparza) in 20 patients with metastatic renal cell carcinoma (RCC) who harbor BAP1 (BRCA1-associated protein 1) or other DNA repair gene mutations, which are known to confer aggressive disease, Ged says. Notably, this is the first and only study evaluating PARP inhibitor monotherapy in patients with advanced RCC. The study was enriched for patients with BAP1 mutations because it confers sensitivity to DNA damage repair agents like PARP inhibitors.

Eligible patients received 150 mg of oral olaparib twice daily for 4 weeks for the safety run-in considering the possibility for kidney injury, followed by 300 mg of olaparib twice daily until disease progression, unacceptable toxicity, or patient withdrawal, Ged says. The primary end point of the study is disease control rate, which included complete response, partial response (PR), and stable disease (SD) for at least 6 months. 

Interim findings, which were presented at the 2023 Kidney Cancer Research Summit, demonstrated that 13 patients had been enrolled to date. Most patients were heavily pretreated, having received more than 3 prior lines of therapy, Ged says. Additionally, all patients received prior immunotherapy, Ged says. Notably, the predefined threshold for efficacy was met, Ged says.

Among 11 evaluable patients, 2 patients achieved disease control and 3 experienced tumor shrinkage. Additionally, 2 patients who achieved durable deep PR and SD, respectively, had a BAP1 mutation, supporting the idea that this class of agents may be effective in this population. Regarding safety, olaparib was well tolerated with minimal grade 3 or greater adverse effects. Limited kidney toxicity was seen with olaparib, Ged concludes.