Dr Yap on the Continued Investigation of Saruparib in Advanced Solid Tumors

Timothy Yap, MBBS, PhD, FRCP, medical oncologist, physician-scientist, professor, Department for Investigational Cancer Therapeutics (Phase I Program), Department of Thoracic/Head and Neck Medical Oncology; vice president, head, clinical development, Therapeutics Discovery Division; associate director, translational research, Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, discusses next steps for investigating saruparib (AZD5305) in patients with advanced solid tumors, including prostate cancer, that harbor genetic mutations.

Future investigations of saruparib involves will expand across various cancer types and genetic mutations, Yap begins. This drug’s potential goes beyond its current scope, necessitating comprehensive exploration in diverse oncological settings, he says. Saruparib is currently being evaluated in the phase 3 EvoPAR-PR01 clinical trial (NCT06120491) in patients with prostate cancer, where it will be used in combination with new hormonal agents, Yap explains, adding that other studies are also planned to further understand and establish the drug’s efficacy and safety profiles.

Notably, in the phase 1/2a PETRA trial (NCT04644068), the most common genetic alterations observed were BRCA1 and BRCA2 mutations, followed by PALB2 and RAD51C/D mutations, he continues. As expected, these mutations were prominent in the patient population, but differentiating the efficacy of saruparib across these mutations has proven challenging, according to Yap. This is an area that will require more in-depth investigation in future studies, Yap elucidates. Understanding these differences is crucial for tailoring treatments to individual genetic profiles and optimizing therapeutic outcomes, he notes.

Saruparib is a first-in-class PARP1 selective inhibitor, set apart from already-approved first-generation PARP1 and PARP2 inhibitors. This new class of PARP1 selective drugs holds the promise of significantly enhanced efficacy, Yap expands. The rationale behind this optimism lies in the selective targeting mechanism of these agents, which potentially offers a higher therapeutic index, Yap notes. Saruparib has been associated with a promising safety profile in preliminary studies, alongside favorable pharmacokinetic and pharmacodynamic characteristics, he concludes.