Clovis Oncology’s PARP Inhibitor Shines in Preliminary Prostate Cancer Trial

At the virtual AACR conference 2021, Boulder-based Clovis Oncology presented encouraging results from its Phase 1b RAMP trial that evaluated the combination of its Rubraca (600 mg twice daily) with Pfizer/Astellas’ Xtandi (160 mg once daily) for the treatment of advanced prostate cancer. Results from the study show that the combination yielded promising signs of antitumor activity. Besides, the safety, a primary endpoint of the study, was comparable to that of each drug when used as monotherapy.

“We remain committed to understanding how Rubraca may benefit patients with cancer, and the data presented at AACR further enhance our understanding in different patient populations and solid tumor types,” said Patrick J. Mahaffy, President, and CEO of Clovis Oncology.

Exploring Synthetic Lethality in Cancer

Rubraca, a PARP inhibitor, is FDA approved as a monotherapy treatment for BRCA1/2-mutant, metastatic Castration-Resistant Prostate Cancer (mCRPC). Xtandi, an androgen receptor antagonist, is also approved for treating mCRPC and metastatic castration sensitive prostate cancer (mHSPC).

Since preclinical studies have shown that the combination of androgen receptor-directed therapy and PARP inhibitor can result in synthetic lethality in prostate cancer, Clovis attempted to evaluate the combination in unselected patients with mCRPC.

Change from baseline in Prostate-Specific Antigen (PSA) levels was one of the secondary endpoints of the study. Six out of eight patients who had progressed on androgen receptor-directed therapies showed a decline in PSA levels from baseline. Among them, four had a confirmed PSA response. Interestingly, these declines were observed even in the presence of androgen receptor alterations and the absence of DNA damage repair gene alterations.

“The Phase 1b RAMP data for the combination of Rubraca and Xtandi in unselected mCRPC patients help inform the Alliance for Clinical Oncology-sponsored CASPAR Phase 3 trial, which is expected to begin enrolling patients soon, and we look forward to learning more about the combination,” said Mahaffy.

Clovis also presented encouraging Phase 1 data from the RUCA-J study, which evaluated Rubraca in Japanese patients with advanced solid tumors, including ovarian, prostate, endometrial, and pancreatic cancer. Results showed that Rubraca (600 mg twice daily) was safe in Japanese patients and the PK profile overlapped with that of western patients.

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Rajaneesh K. Gopinath