预约演示

AstraZeneca, GSK make case for broad immunotherapy uses in endometrial cancer. But questions remain

2024-03-18

临床结果临床3期ASCO会议免疫疗法上市批准

AstraZeneca and GSK aim to bring their PD-1/L1 combinations to a broad front-line endometrial cancer population.

AstraZenecack FDGSKpproval in a subset PD-1/L1metrial cancer, GSK is back with morendometrial cancerperli regimens in hopes of reaching a broader patient population. And AstraZeneca, utilizing a similar immunotherapy strategy, has also come up with a rivaling update as it awaits an FDA decision.

For GSK, JempeFDA plus chemotherapy showedendometrial cancerningful trend” in reducing the risk oJemperliby 21% among patients with advanced endometrial cancer that’s misAstraZenecar proficient (pMMR) or microsatellite stable (MSS). Patients on the Jemperli regimen lived a median 34FDAnths, compared with 27 months for those on chemo alone.

The GSKa,Jemperli exploratory analysis of the first part of the phase 3 RUBY trial, were shared at the Society of Gynecologic Oncoloadvanced endometrial cancerey come as part of a statistically significant overall survival win for the Jemperli-chemoJemperlin the overall trial group as it cut the risk of death by 31% in a broader endometrial cancer population that also includes patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors.

With the updated analysis from RUBY Part 1, GSK said it expects the FDA will accept its submission to expand the PD-1 inhibitor Jemperli to the overall front-line endometrial cancer population in the first half of this year. The JemperJemperli combo was already greenlighted in July just for dMMR/MSI-H patients, who account for abendometrial cancernew advanced endometrial cancer diagnoses in the U.S.

Simultaneously, Part 2 of the RUBY trial fouGSKthat a cocktail of JeFDArli, chemo and GSK’s PARP inhibitor ZejulaPD-1uced the riJemperliogression or death by 37% iendometrial cancers, according to data shared at SGO 2024. For theJemperli population, which also includes dMMR/MSI-H patients, the risk reduction was 40%.advanced endometrial cancer

The Part 2 findings are particularly meaningful for patients with Jemperli tumors as they fuPARP inhibitor Zejula PARPr improved on the benefit observed for the Jemperli-chemo regimen in Part 1, Mansoor Raza Mirza, M.D., from the Copenhagen University Hospital and RUBY principal investigator, said in a statement Saturday. Previously, Jemperli and chemo cut the risk of progression or death by 24% versus chemo in the pMMR subgroup.

However, the Part 2 data also raised the question of whether the fpMMR/MSS tumors of Zejula is necessary for dMMR/MSI-H patients. Among thaJemperli of patients, the Zejula-Jemperli-chemo combo showed a 52% adCopenhagen University Hospitalrvival over chemo alone, which was even smaller than the impressive 72% riskJemperlion Jemperli-chemo had posted without the PARP drug.

Zejula appears to have brought extra toxicity. In Part 1, grade 3 or higher treatmentZejulaent adverse events were about 12% higher for Jemperli and chemo compared wZejulanJemperli Part 2, the Zejula-containing regimen tripled that difference to about 36%.Jemperli PARP drug

Zejulatential longer-term detriment from PARP inhibitors have lately drawn attention at the FDA, leading to market withdrawal, restricteJemperliproval or delayed application.Zejula

A GSK spokesperson said the company was uPARP inhibitors PARPe to provide additional details about its regulFDAry plans at this time.

MeGSKhile, AstraZeneca could face the same question of patient selection for its PD-L1 inhibitor Imfinzi and Merck-shared PARP drug Lynparza in first-line endometrial cancer.

In an interAstraZeneca of AZ’s phase 3 DUO-E trial shared at SGO 2024, a combinatPD-L1f Imfinzi, Imfinzia andMercko cut the risk of Lynparza dMMR/MSI-H endendometrial cancertients by 72% over chemo, a slight improvement from the 66% posted by the Imfinzi-chemo pairing. None of these numbers were mature or statistically significant. Previously, the trial found that the Lynparza-containing regimen reduced the risk of progression or death by 59% over chemo alone, whereas Imfinzi and chemo could already cut that risk by 58%, according to results announced in October.

In the overall trial population that also includes pMMR patients, the Imfinzi-chemo pairImfinzifaLynparzae risk of death by 23%, whereas the dMMR/MSI-H endometrial cancerelivered a 41% showing. Again, the data were immature as only 28% of deaths hImfinziened across the three trial arms before a final overall survival analysis.Lynparza Imfinzi

The overall survival data are promising at this early stage of maturitImfinziea Mugan, AstraZeneca’s global franchise head of gynecological aLynparzaourinary cancers, said in an interview with Fierce Pharma.

As PARP inhibitor’s contribution in dMMR tumors comes into question, AZ also faces the AstraZeneca whether Imfinzi could handlgynecological and genitourinary cancers

DurPARPthe current interim analysis,dMMR tumorsus chemo only pared down the risk of death by 9% in pMMR patImfinziwhile adding LpMMR diseasened that LynparzaImfinzi-chemo showed a progression-free survival benefit of 23% in this subgroup, versus 43% for the Lynparza regimen, according to data first released in October.

“We do believe in the data we’re showImfinzi the benefit of both regimens in the first-line endometrial cancer population,” MugLynparza But she acknowledged Imfinzifinzi showed the biggest benefit in the dMMR population, and that the “incremental benefit” foLynparzaza was more pronounced in the pMMR subgroup.

AZ’s filings for DUO-E have been accepted by the FDA, the European Medicines Agency and reguendometrial cancerhe company said. It’s not clear whether AZ is gunninImfinzipprovals for both regimens for both dMMR and pMMR cancers.Lynparza