Perhaps PD-1 inhibitors just aren’t for ovarian cancer after all.
Days after Merck & Co. posted a disappointing result on patient survival from its PD-1/PARP combination of Keytruda and Lynparza in ovarian cancer, GSK delivered a similar message for its Jemperli-Zejula cocktail.
The addition of Jemperli to chemotherapy and Zejula maintenance—with or without Avastin—failed to significantly extend patients’ lives in first-line advanced ovarian cancer, GSK said Friday.
The readout came from the phase 3 FIRST trial, which is technically positive because it met its primary endpoint, showing a statistically significant disease-progression benefit for the addition of Jemperli. Overall survival served as a key secondary endpoint.
In its announcement, GSK said it’s running further analyses and plans to share the data with health authorities and the scientific community at an upcoming meeting.
The FIRST readout comes later than expected, but its outcome is not exactly a surprise. During an interview with Fierce Pharma in January 2023, GSK’s chief commercial officer, Luke Miels, acknowledged that the FIRST study had a low chance of success because ovarian cancer isn’t immunogenic and therefore might not respond well to immune checkpoint inhibition by Jemperli.
A few days ago, Merck lent evidence to that conjecture with a readout from the phase 3 KEYLYNK-001 trial in first-line ovarian cancer. There, Keytruda’s addition to Lynparza maintenance—plus chemo, with or without Avastin—also failed to move the overall survival needle despite a progression-free survival win. The Merck trial focuses on BRCA nonmutated tumors.
In its statement, Merck said the role of Keytruda in this PD-L1 expression-agnostic population “remains uncertain.”
BRCA nonmutated disease is the main target for the two companies’ ovarian cancer trials utilizing their PD-1 inhibitors, because PARP drugs such as Lynparza and Zejula are already standard first-line maintenance treatments among BRCA-mutated patients.
Between the two leading PARP inhibitors, Zejula boasts a broad FDA label in ovarian cancer, allowing it to be used in patients regardless of their biomarker status. However, thanks to a limited efficacy showing, acceptance of Zejula in BRCA nonmutated patients has been low.
This low adoption has been reflected in Zejula’s sales numbers. While it has the nonmutated market all to itself, Zejula only brought in $450 million in sales in the first nine months of 2024. For Lynparza, Merck’s partner AstraZeneca reported $2.2 billion in sales during the same period.
For GSK and Merck, FIRST and KEYLYNK-001 represent their respective bids to convince doctors of the benefit of using PARP inhibitors in BRCA nonmutated ovarian cancer—while also potentially expanding the reach of their PD-1 inhibitors.
But there was one more goal for GSK. The British pharma was also not-so-secretly hoping that the FIRST study could indirectly show Jemperli as a better PD-1 inhibitor than Merck’s leading Keytruda. That hope seems shattered now that both drugs have failed on the overall survival endpoint. That is, unless detailed data from the two trials show a marked difference in the magnitude of disease progression benefit in favor of Jemperli.