Liquid Biopsy Test Helping Select People with Advanced Prostate Cancer for Phase 2 Study of Pamiparib

A Phase 2 trial testing the investigational PARP inhibitor pamiparib in treating metastatic castration-resistant prostate cancer patients is using Epic Sciences‘ novel liquid biopsy assay to select those patients who are most likely to benefit from treatment, the company announced.

Epic’s test is designed to collect circulating tumor cells from a simple blood draw. Cells are then counted and examined for defects in DNA repair, which makes them more responsive to PARP inhibitors like pamiparib.

In cancer, major chromosomal alterations that lead to poor prognosis, cancer spread, and treatment resistance are often associated with defects in one of the mechanisms of DNA repair – called homologous recombination.

Epic examines circulating tumor cells (CTCs) for homologous recombination deficiency (HRD) by simply looking into major alterations in chromosomal number and size – a feature called chromosomal instability.

“This is the first assay to measure chromosomal instability using circulating tumor cells and digital pathology [a technology that converts microscopy samples into digital data], opening up tremendous opportunities for developers of anticancer PARP inhibitors to improve patient selection in clinical trials,” Ryan Dittamore, chief of medical innovation at Epic Sciences, said in a press release.

“The ability to track this key mechanism of cancer progression within patients through a simple blood draw not only predicts when patients will not respond to standard of care therapy, but also who should consider therapies that target DNA repair pathways,” he added.

Until now, it has been challenging to measure chromosomal instability in tumor biopsies, as not many cells in the primary tumor have this feature. Epic’s liquid biopsy assay was designed to address this problem.

Working in collaboration with BeiGene, the company is now testing the potential of its liquid biopsy assay – called Epic Sciences CTC HRD assay – in enrolling a responsive patient group in the ongoing and open-label Phase 2 trial (NCT03712930) for men with metastatic castration-resistant prostate cancer.

The study is assessing BeiGene’s experimental PARP inhibitor pamiparib in men whose circulating tumor cells are positive for homologous recombination deficiency.

Currently recruiting patients in Australia and Puerto Rico, the trial is expected to enroll about 100 people. Its main goal is to determine the number of patients responding to pamiparib treatment, and secondary goals include duration of response, and time to response.

“We are excited to be at the forefront of the development of this novel CTC HRD assay with our global Phase 2 trial of pamiparib in patients with metastatic castration-resistant prostate cancer,” said Mitch Raponi, vice president of BeiGene.

The company had previously developed the Oncotype Dx AR-V7 Nucleus Detect test, which detects if castration-resistant prostate cancer patients have a targetable variant of the androgen receptor. This helps to determine if patients should receive chemotherapy or treatment with androgen receptor-directed therapies. Oncotype is now commercially available in the U.S. and is reimbursable by Medicare.