Myriad Genetics announces new clinical studies on myChoice HRD companion diagnostic test at ASCO 2015

Predicts Response to PARP inhibitors and Platinum-based Drugs in Clinical Studies

Myriad Genetics, Inc. (NASDAQ: MYGN) today announced new clinical studies on its myChoice HRD companion diagnostic test at the 2015 American Society of Clinical Oncology annual meeting being held in Chicago, Ill.  

Myriad’s myChoice HRD test is the first and only companion diagnostic to measure three modes of homologous recombination deficiency (HRD) including loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions in cancer cells. The myChoice HRD score is a biomarker that indicates the inability of cancer cells to repair DNA damage and reflects a tumor’s sensitivity to DNA-damaging medicines such as PARP (poly-ADP ribose polymerase) inhibitors and platinum-based therapies.

“The myChoice HRD companion diagnostic test stems from Myriad’s pioneering research and is a real step forward in realizing the goal of personalized medicine for patients with ovarian, breast and pancreatic cancers and possibly other solid tumors,” said Jerry Lanchbury, Ph.D., chief scientific officer, Myriad.  “Anybody who has ever had cancer or treated patients with cancer will understand the enormous benefit of getting the right treatment to the right patient at the right time. There is mounting evidence that myChoice HRD can help us do that by predicting a therapeutic response to DNA-damaging agents based on patients’ unique tumor biology.”  

Below are the key myChoice HRD presentations being highlighted at #ASCO15.

myChoice HRD:  Predicting Platinum Response

Poster Discussion (Poster 32): Combined Homologous Recombination Deficiency (HRD) Scores and Response to Neoadjuvant Platinum-Based Chemotherapy in Triple Negative and/or BRCA1/2 Mutation-Associated Breast Cancer.

Melinda Telli, M.D. (Stanford University School of Medicine) will present new clinical data that established a homologous recombination (HR) deficiency threshold that can identify 95 percent of patients with mutations in BRCA1/2 and other homologous recombination genes and who have a higher likelihood of responding to treatment with DNA-damaging agents. Specifically, the study validated an HRD threshold score of ≥42 (on a scale of 0-100) using a training cohort of 497 breast and 561 ovarian cancer patients. A myChoice HRD test score ≥42 represents a positive score or a loss of DNA repair function, while a myChoice HRD score <42 reflects a negative score or an intact DNA repair function.

Using this threshold, the myChoice HRD test was then evaluated to predict response to neoadjuvant platinum-based chemotherapy in patients with TNBC or BRCA1/2 mutation-associated breast cancer. The endpoints of this analysis were residual cancer burden (RCB) and pathological complete response (pCR). The results showed that a positive myChoice HRD score and/or a BRCA1/2 mutation were statistically significantly associated with treatment response (Table 1), and importantly, the myChoice HRD test identified responders lacking a deleterious BRCA1/2 mutation. In this study, myChoice HRD predicted nearly double the number of patients who would likely respond to neoadjuvant platinum-based chemotherapy compared to BRCA1/2 mutations alone or other clinical features.

Table 1: HR Deficiency Status (N=72)

Podium Presentation (Abstract 1004): Prediction of Pathological Complete Response (pCR) by Homologous Recombination Deficiency (HRD) after Carboplatin-Containing Neoadjuvant Chemotherapy in Patients with TNBC: Results from GeparSixto.

Prof. Gunter Von Minckwitz (German Breast Group, Isenburg, Germany) will show data in a featured podium presentation that demonstrate the ability of the myChoice HRD test to predict pathological complete response (pCR) to platinum chemotherapy in patients with triple negative breast cancer (TNBC).  A total of 193 patients with TNBC who received paciltaxel/liposomal doxrubicin or paciltaxel/liposomal doxrubicin +carboplatin in the GeparSixto trial were evaluated with the myChoice HRD companion diagnostic test using the clinically validated endpoint from the Telli study above.

Of these, 136 (70 percent) patients were myChoice HRD positive due to a high test score and/or a deleterious tumor mutation in the BRCA1/2 (tBRAC) genes, which reflect HRD. Using the original study endpoint (pCR = ypT0 ypN0), the highest response rate in the primary analysis of 63.5 percent was observed in patients who were myChoice HRD positive and were treated with carboplatin/standard-of-care (Table 2). Importantly, in a supplemental analysis, the statistically significant response rate remained in patients who were myChoice HRD positive but had no mutation in the BRCA1/2 genes (Table 3). These data indicate that myChoice HRD is a highly sensitive biomarker, regardless of the cause of HRD, and support using the myChoice HRD test to identify patients who are likely to respond to DNA-damaging agents like carboplatin.

Table 2: All Tumors (pCR = ypT0 N0)

Table 3: myChoice HRD Positive (pCR = ypT0 N0)

myChoice HRD:  Predicting PARP Inhibitor Response

Poster 90: Homologous Recombination Deficiency (HRD) Score Enriches for Niraparib Sensitive High Grade Ovarian Tumors.

A presentation by Keith Wilcoxen, Ph.D., (Tesaro, Inc.), will show how BRCA status and HR-deficiency were assessed in ovarian tumors using the myChoice HRD test to predict response to treatment with niraparib, an investigational PARP inhibitor currently in Phase 3 clinical studies being conducted by Tesaro. In this Phase 3 clinical study, a myChoice HRD positive score of ≥42 was used to determine loss of DNA repair function, while a myChoice HRD negative score <42 reflected intact DNA repair function.  A total of 106 tumors from patients with advanced ovarian cancer were evaluated for HRD and BRCA1/2 mutations.  

The results showed that all BRCA deficient tumors (n=26) were myChoice HRD positive except one. Additionally, the response to niraparib monotherapy was evaluated in 20 unique tumor models across a range of myChoice HRD scores and all of the tumors that responded to niraparib were myChoice HRD positive, irrespective of BRCA deficiency status.  

These data further confirm that the myChoice HRD companion diagnostic test is predictive of BRCA deficiency and support its use to help identify patients with advanced ovarian cancer who may respond to treatment with niraparib.