AstraZeneca and Merck plan on seeking regulatory approval for Lynparza as a treatment for a subset of prostate cancer patients based on the Phase III PROfound data.
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During the American Society of Clinical Oncology meeting in June, Olivier Nataf, head of AstraZeneca’s U.S. oncology business unit, told BioSpace that AstraZeneca was “here to stay” as an oncology company, primarily due to the consistent performance from the PARP inhibitor Lynparza.
This morning, U.K.-based AstraZeneca and its development partner Merck announced that Lynparza has notched another impressive late-stage study on its belt. Data from the Phase III PROfound trial showed Lynparza (olaparib) hit its endpoints in men with metastatic castration-resistant prostate cancer (mCRPC) who have a homologous recombination repair gene mutation (HRRm) and have progressed on prior treatment with new hormonal anticancer treatments. Results from the trial showed a statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival with Lynparza versus enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations, a subpopulation of HRR gene mutations.
Lynparza is a first-in-class PARP inhibitor. It is the first targeted treatment that blocks DNA damage response in cells and tumors that have a deficiency in homologous recombination repair (HRR), such as BRCA1 and BRCA2 mutations.
Prostate cancer is the second-most common cancer in men. mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these will have metastases at the time of CRPC diagnosis.
Full data from the PROfound trial will be presented at a future medical conference, the companies said this morning. But in the meantime, Merck and AstraZeneca are already planning to discuss the late-stage results with regulatory agencies across the globe in hopes of approval. The companies are also exploring additional trials in prostate cancer, including the ongoing Phase III PROpel trial, testing Lynparza as a first-line therapy in mCRPC, in combination with abiraterone, a common hormone therapy for the treatment for prostate cancer that has spread to other parts of the body.
José Baselga, head of oncology at AstraZeneca, noted that for men with mCRPC, the disease is deadly with a poor prognosis, particularly for those patients who have not seen success with hormonal anticancer treatments. Baselga said the PROfound trial is the “only positive Phase III trial of any PARP inhibitor in metastatic castration-resistant prostate cancer.” He added that the Phase III trial demonstrated the potential value of genomic testing in this at-risk patient population.
“Metastatic castration-resistant prostate cancer is a deadly disease and represents an area of critical unmet medical need. The Phase III PROfound trial is another example of MSD and AstraZeneca’s shared commitment to improving long-term outcomes for people living with cancer. These results represent the potential for a new, oral targeted treatment option for this patient population,” Roy Baynes, Merck’s head of global clinical development and chief medical officer for MSD Research Laboratories said in a statement.
At ASCO earlier this year, AstraZeneca and Merck presented strong Lynparza data in pancreatic cancer. In patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas. Lynparza reduced the risk of disease progression by 47 percent compared to placebo. The company is seeking approval of Lynparza for this indication. In December, Lynparza won approval from the U.S. Food and Drug Administration for use as a first-line maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to 1st-line platinum-based chemotherapy.
