Clovis hopes to get ahead of rivals in prostate cancer with Rubraca

Clovis’ PARP inhibitor drug Rubraca is showing promise in prostate cancer, according to data released at this year’s ESMO conference, as the company hopes to steal a march on AstraZeneca and Merck & Co’s more established rival drug.

Several poly (ADP-Ribose) polymerase (PARP) drugs are on the market, after AstraZeneca and Merck & Co’s Lynparza (olaparib) was first approved in ovarian cancer in 2014.

Manufacturers of these drugs are carving themselves a niche in certain cancers with mutations that respond to the drug, which works by interfering with cancer cells’ DNA repair system, eventually causing them to self-destruct.

US biotech Clovis is one of those competitors, after getting its PARP drug Rubraca (rucaparib) approved in ovarian cancer in late 2016.

But Clovis is also chasing other indications, with prostate cancer the most promising so far, with the FDA designating the drug as a Breakthrough Therapy in a subset of patients.

At the European Society for Medical Oncology (ESMO)conference in Munich Clovis unveiled early data from its TRITON2 trial, which tested Rubraca as a monotherapy in adults with BRCA1/2 mutated metastatic castration-resistant prostate cancer, who have received at least one prior androgen receptor therapy and taxane-based chemotherapy.

The results from TRITON2, a single arm phase 2 trial involving 85 patients, were enough to earn Clovis the breakthrough designation, setting up a potential fast six-month review if results go well.

Early data from the trial presented at ESMO showed a 44% confirmed response rate based on a sample of 25 patients evaluable using standard criteria.

There was a 51% confirmed response rate in 45 patients evaluable using prostate-specific antigen tests, who had a BRCA1/2 alteration.

There were also reductions in lesion diameters and PSA measurements in patients with a mutation known as ATM.

Only around 12% of mCRPC patients have the BRCA1 or BRCA2 mutations, but there is also the possibility of identifying patients with a patient-friendly cell-free circulating tumour DNA test.

Experts at the conference were optimistic about the drug’s potential in prostate cancer.

Professor Markus Joeger, of Kantonsspital, St Gallen, Switzerland told pharmaphorum in an interview on the sidelines of the conference: “I have no doubt that this will get approved and that it will be quite an important treatment for prostate cancer patients. The next stage will be to look more closely at the response.”

Dr Joaquin Mateo, of the Prostate Cancer Translational Research Group, at the Vall d’Hebron Institute of Oncology, said in a poster presentation that the drug showed “promising antitumour activity”.

However there is a need for a longer follow-up to better assess the magnitude of effect, and a more data to understand patients with other DNA repair mutations other than BRCA1/2, he added.

Joeger agreed with this analysis, adding: “The issue is what is the best biomarker?”

In the longer term, Clovis is running a phase 3 trial, TRITON3, comparing Rubraca with the blockbuster prostate cancer drugs from Janssen and Pfizer – Zytiga (abiraterone) and Xtandi (enzalutamide) – in a bid to further expand the eligible patient group.

 

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