Dr Yap on the Investigation of Saruparib in 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 the rationale for investigating saruparib (AZD5305) in patients with advanced solid tumors and genetic mutations.

Currently, there are 4 approved PARP inhibitors in clinical use that have demonstrated effectiveness and benefits for patients with cancer. However, these inhibitors are associated with a range of adverse effects (AEs), including fatigue, myelosuppression, and gastrointestinal issues, Yap begins. Given these AEs, there is a significant need to develop drugs that maintain high efficacy with minimal AEs, he states.

All currently approved PARP inhibitors target both PARP1 and PARP2 and act as trappers of these enzymes. The hypothesis driving the development of saruparib is that selectively inhibiting PARP1, without affecting PARP2, could achieve the desired therapeutic effects with fewer AEs, Yap continues. Saruparib is a first-in-class selective PARP1 inhibitor.

The clinical development of saruparib was undertaken through the phase 1/2a PETRA trial (NCT04644068), he expands. The trial consists of a dose-escalation phase followed by a dose-optimization expansion phase. During the dose-escalation phase, patients with breast, ovarian, prostate, and pancreatic cancers were enrolled, Yap details.

The trial was designed with flexible hemoglobin requirements and explored saruparib doses ranging from 10 mg to 140 mg administered once daily. This study approach aimed to determine the optimal dose of the agent that balances efficacy and safety for further clinical development, he explains. By focusing on a highly selective PARP1 inhibitor such as saruparib, researchers hope to provide a new therapeutic option that offers significant benefits with fewer AEs compared with existing PARP inhibitors, Yap concludes.