Dr. Yap on the study of saruparib in solid tumors

Timothy Yap, MBBS, PhD, FRCP, medical oncologist, physician-scientist, professor, Division of Experimental Cancer Therapeutics (Phase I program), Division of Thoracic, Head and Neck Medical Oncology; Vice President, Chief of Clinical Development, Division of Therapeutics Discovery; Associate Director of Translational Research, Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, discusses the rationale for studying saruparib (AZD5305) in patients with advanced solid tumors and genetic mutations.

There are currently four approved PARP inhibitors in clinical use that have proven their efficacy and benefits for cancer patients. However, these inhibitors are associated with a number of side effects, including fatigue, myelosuppression and gastrointestinal problems, Yap begins. Given these side effects, there is a significant need to develop drugs that maintain high efficacy with minimal side effects, he explains.

All currently approved PARP inhibitors target both PARP1 and PARP2 and act as scavengers of these enzymes. The hypothesis underlying the development of Saruparib is that by selectively inhibiting PARP1 without affecting PARP2, the desired therapeutic effects could be achieved with fewer side effects, Yap continues. Saruparib is the first selective PARP1 inhibitor in its class.

Saruparib’s clinical development was conducted in the PETRA Phase 1/2a study (NCT04644068), he explains. The study 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 cancer were enrolled, explains Yap.

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