AstraZeneca and Merck to Seek Regulatory Approval for Lynparza in Pancreatic Cancer

Olivier Nataf, head of AstraZeneca’s U.S. oncology business unit, is excited about the potential the company’s PARP inhibitor Lynparza is showing as a potential treatment of pancreatic cancer.

Olivier Nataf, head of AstraZeneca’s U.S. oncology business unit, is excited about the potential the company’s PARP inhibitor Lynparza is showing as a potential treatment of pancreatic cancer.

In February, U.K.-based AstraZeneca and its developmental partner Merck & Co. first announced that Lynparza hit its endpoints in the Phase III POLO trial. Data showed that patients treated with Lynparza showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as first-line maintenance therapy alone in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas in patients who haven’t responded to platinum-based chemotherapy. Over the weekend at the American Clinical Society of Oncology, the two companies released additional data that showed how robust the data was. Lynparza reduced the risk of disease progression by 47% compared to placebo. The median PFS for patients treated with Lynparza was 7.4 months, compared to 3.8 months for those on placebo. The companies said there were more than twice as many patients remaining progression free at both one year, 34% to 15% and two years, 22% vs. 10%, respectively.

Speaking with BioSpace ahead of the ASCO presentation, Nataf said this was the first time a PARP inhibitor has demonstrated activity in germline BRCA-mutated metastatic pancreatic cancer. He said the drug could provide hope for patients who are diagnosed with one of the worst cancers you can get. In the POLO trial, Nataf said the results show that more than twice as many patients taking the PARP inhibitor were progression free than those on placebo at six months.

“The five-year overall survival rate of this cancer is 3%. The last time there was a new treatment approved for this cancer was five years ago. It’s a hard cancer to treat. It is just one terrible story after another… eight studies have failed in pancreatic cancer in 2015 and 2016. It is a devastating disease and has such limited options. And this is why we’re so excited about Lynparza,” Nataf said.

Nataf added that the POLO trial results provide further evidence of the clinical benefit Lynparza can have across a variety of BRCA-mutated tumor types.

The companies believe that the POLO results could open the door for more personalized biomarker-led care in metastatic pancreatic cancer, particularly if the BRCA status can be detected early. The Phase III POLO trial randomized 154 patients with gBRCAm metastatic pancreatic cancer that had not progressed on first-line platinum-based chemotherapy. Patients were randomized three-to-two to receive Lynparza or placebo until the disease progressed.

Early diagnosis of pancreatic cancer is difficult, as often there are no symptoms until it is too late. Around 80% of patients are diagnosed at the metastatic stage.

Based on the results from this trial, AstraZeneca and Merck are seeking regulatory approval of Lynparza for this indication. 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. Lynparza has shown efficacy against mutations of the BRCA gene. While not yet approved for gBRCAm pancreatic cancer, the drug has been approved for as first-line maintenance treatment in BRCAm advanced ovarian cancer, as well as for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy.

“Our team is dedicated to its mission to make an impact in spaces like this, which is just an incredibly upsetting disease. Again and again, Lynparza shows benefits and medicated outcomes in patients” Nataf said.