AstraZeneca adds endometrial cancer to Imfinzi-Lynparza combo's positive trial readouts

Shortly after touting a win in ovarian cancer, AstraZeneca trotted out positive news for its combination of Imfinzi and Lynparza in an endometrial cancer trial, too.

A regimen containing AZ’s Imfinzi, either by itself or used with Lynparza, topped chemotherapy at preventing tumor progression or death in patients with newly diagnosed advanced or recurrent endometrial cancer, the British pharma said Friday.

The positive phase 3 readout from the DUO-E trial comes a few months after GSK’s Jemperli and Merck & Co.’s Keytruda celebrated their own triumphs in first-line endometrial cancer. But AZ is the first to have used a PAPR inhibitor, namely, Lynparza.

In both Keytruda’s NRG-GY018 trial and Jemperli’s RUBY study, investigators used each PD-1 inhibitor first in tandem with chemo and then by itself as maintenance. In DUO-E, patients in the experimental arm also initially received Imfinzi and chemo. But during the study’s maintenance phase, AZ instead tested either Imfinzi monotherapy or its combination with Lynparza. In all three trials, patients in the control arms only received initial chemotherapy as active treatment.

Given that both Imfinzi alone and its Lynparza combo showed significant progression-free survival advantage over the chemo arm, doctors would want to know whether Lynparza is necessary. For now, AZ said researchers observed a “greater clinical benefit” for the combination.

AZ will have a high bar to meet based on what GSK and Merck have shown for their own immunotherapies.

In RUBY, Jemperli cut the risk of progression or death by 72% in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. The number was 24% in non-dMMR/MSI-H patients.

In NRG-GY018, Keytruda’s risk reduction reached 70% in the dMMR/MSI-H group and 42% in the other patients after a relatively short follow-up time.

As for whether the drugs could extend patients’ lives, none of the three trials have mature overall survival data. AZ said investigators at this point observed a positive trend favoring the two Imfinzi regimens.

The endometrial cancer win also follows a positive phase 3 readout for the Imfinzi-Lynparza combo in ovarian cancer. Adding the combo to chemotherapy and Roche’s Avastin significantly improved progression-free survival for newly diagnosed ovarian cancer without BRCA mutations in the DUO-O trial.

However, the FDA has recently hyped scrutiny over the PARP inhibitor class which has led to several indication withdrawals. SVB Securities analyst Daina Graybosch, Ph.D., suggested that AZ will face a tough review for the DUO-O indication.

Detailed DUO-O results are slated to be presented on June 3 at the 2023 American Society of Clinical Oncology annual meeting.

AZ said it will also discuss the new DUO-E data with regulators. AZ is partnered with Merck on Lynparza, but the two do separate trials when their PD-1/L1 inhibitors are involved.

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