Phase 1 Trial for SNV1521 PARP1 Inhibitor in mCRPC aka mAPMR Prostate Cancer

A next-generation PARP inhibitor called SNV1521 is showing early signs of activity in advanced prostate cancer, while potentially causing less bone-marrow toxicity than existing PARP drugs.

SNV1521 is an oral drug designed to selectively inhibit PARP1 while largely sparing PARP2. Current PARP inhibitors such as olaparib inhibit both proteins, and suppression of PARP2 is thought to contribute to anaemia and other haematological side effects. Greater selectivity could therefore allow stronger or more sustained PARP inhibition with better tolerability.

The ongoing phase 1 trial enrolled patients with advanced solid tumours, including metastatic castration-resistant prostate cancer (mCRPC). In the first reported dataset, 32 patients had been treated, including six with prostate cancer. Two of those six men achieved PSA responses, and both had BRCA2 alterationss, one germline and one somatic.

Across the broader study, SNV1521 achieved more than 90% PARP inhibition at doses of at least 10 mg per day. Among 14 patients evaluable by RECIST, 11 (78%) experienced some degree of tumour shrinkage, although this figure includes several different cancer types and should not be interpreted as a prostate cancer response rate.

Early safety results are also encouraging. No dose-limiting toxicities were observed and the maximum tolerated dose had not been reached. The most common treatment-related adverse events were fatigue and nausea, both at 19%, neutropenia at 16% and thrombocytopenia at 13%. Almost all were grade 1–2, with no grade 4 or higher treatment-related events reported.

The prostate cancer programme is now expanding. An Australian centre participating in the study recently reported that six men with heavily pretreated prostate cancer have received SNV1521, with tumour growth reportedly stopped or slowed, and recruitment is continuing for additional patients.

Six prostate cancer patients are far too few to establish efficacy, but the combination of early antitumour activity and relatively limited haematological toxicity makes SNV1521 an interesting drug to follow.

Source.

Clinical trial.