Collaborators Aim to Identify OC Patients Likely to Benefit from New Combo Therapy

Collaborators Aim to Identify OC Patients Likely to Benefit from New Combo Therapy

The University of New Mexico (UNM) Comprehensive Cancer Center and the New Mexico Alliance for Cancer Care have entered a collaboration with Personalis to use its cancer immunogenomics platform to identify which ovarian cancer patients respond to a new combination therapy — Lynparza (olaparib) plus the investigational immunotherapy tremelimumab.

The combination is being tested in an ongoing Phase 1/2 clinical trial (NCT02571725) in women with BRCA-mutated epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who received at least one prior course of platinum-based chemotherapy.

The study, led by Sarah Adams, MD, associate professor at the UNM Comprehensive Cancer Center, is recruiting 50 patients across five sites in the United States. Find more information here.

“We are delighted to collaborate with Personalis on this study,” Adams said in a press release. “Comprehensive immuno-profiling will inform on biomarkers of response for this experimental treatment in women with BRCA1 or BRCA2 [inherited] mutated ovarian cancers, for which there aren’t standard curative measures.”

Treatment with PARP inhibitors such as Lynparza has become an exciting new approach for ovarian cancers, particularly those with mutations in DNA repair genes, such as BRCA1 and BRCA2. In cancer treatment, blocking PARP keeps cancer cells from repairing their damaged DNA, causing them to die.

In ovarian cancers, these treatments extend the time patients live without their disease getting worse, but they have largely failed to improve overall survival.

In a 2015 study, Adams and her team found that by killing ovarian cancer cells, PARP inhibitors create a highly immunogenic environment, which can make tumors sensitive to immune therapy.

Simply put, the release of cancer particles after treatment with PARP inhibitors attracts immune cells to the cancer location, but because cancer cells often find a way to shut down the activity of these immune cells, activating them would be an efficient way to fight cancer.

In mouse models of ovarian cancer, a combination of Lynparza and an immune checkpoint inhibitor targeting the CTLA-4 molecule worked particularly well, extending survival and creating an immune memory that eliminated cancer cells over 60 days after treatment completion.

In the Phase 1/2 trial, researchers are examining a combination of Lynparza and the investigational CTLA-4 inhibitor tremelimumab, in development by AstraZeneca.

But because tumors have mechanisms to evade immunotherapies, it is imperative to identify biomarkers that predict patients likely to benefit from the combination.

Personalis has developed a platform, called ImmunoID NeXT, that can profile more than 20,000 genes from a single tumor sample. The aim is to unveil the immune repertoire of tumors and their microenvironment that allows cancer cells to evade immune detection and resist immune responses.