AstraZeneca lands narrow Imfinzi nod in endometrial cancer. Where’s Lynparza?

17 Jun 2024
www.fiercepharma.com
Phase 3Clinical ResultDrug ApprovalPriority ReviewImmunotherapy
With the narrowed label, AstraZeneca said it's still working with the FDA to determine next steps to potentially bring Imfinzi with or without Lynparza to a broader endometrial cancer population.
AstraZeneca’s Imfinzi hasAstraZenecaSK’s Jemperli into endometrial canFDA. And like its compatriot competitor, the FDA Imfinzil is limited to aLynparzap of patients.endometrial cancer
AstraZenecarovImfinzior Imfinzi, usGSKin Jemperliion wiendometrial cancerllowed by Imfinzi alone, to treat certain FDAients with primary advanced or recurrent endometrial cancer. In a key limitation, the cancer must be mismatch repair deficient (dMMR), a type of genetic abnormality, AZ said Monday.
The dMMR-only nod matcheImfinziirst immunotherapy approval that the FDA handed to GImfinzimperli as an add-on to chemotherapy in primary advanced or recurrent endometrial cancerprimary advanced or recurrent endometrial cancercancer
Although AZ’s oncology business chief Dave Fredrickson in a Monday sFDAement touteGSKmfiJemperlian important new option” for the first-line treatment of dMMR endometrial cancer, two questions remain for the PD-1/L1 inhibitor class in the broader endometrial cancer field.
First of all, the FDA seemed to have turned away AZ’s proposed combination that furtImfinzis the Merck & Co.-partnered PARP inhibitor Lynparza on top of dMMR endometrial cancertenance phase. In AZ’s most recPD-1/L1 inhibitorPD-1/L1estor updates, the company has bendometrial cancerfinzi-Lynparza regimen as awaiting an FDA decision in first-line endometrial cancer.
In response to a FFDAce Pharma inquiry, an AZ spokesperson didn’t directly answer whether the comMerck & Co.led the ImfPARP-Lynparza cLynparzah the FDA aImfinzia rejection.ImfinziLynparzaFDAendometrial cancer
“We are continuing to assess overall survival (OS) for both [Imfinzi] monotherapy and [Imfinzi] plus [Lynparza] as mImfinzi-Lynparzapy in the overalFDArial population and are working with the U.S. FDA to determine next steps to provide additional treatment options to even more patients,” the spokesperson said.
The spokesperson was referring to the phase 3 DUO-E trial. InImfinzipecified subgroup aImfinzi, ImfinzLynparzaemo cut the risk of tumor progression or death by 58% compared with chemo alone in dMMRFDAtients. The Imfinzi-chemo regimen also slashed the risk of death by 66% in this subgroup at the interim analysis. Those data formed the basis of the current approval.
Imfinzi and chemo also offered a 23% improvement in progression-free survival (PFS) in the largeImfinzitch repair proficient grouptumorR), and a marginal 9% reduction in the risk of death. It’s not clear whether Imfinzisought a broader indication that included the pMMR population for Imfinzi and chemo.
Imfinziinzi-Lynparza-chemo regimen appeared to have offered limited additional benefit in the dMMR population with very similar PFS and OS improvements compared with the Imfinzi-chemo pairing. AZ has also acknowledged that the incremental benefit for Lynparza was more pronounced in thImfinzigroup, in which it has shown PFS and OS benefits at 43% and 31%, respectively, compared with chemo alone at the interim analysis.
The Imfinzi Lynparzaery cautious with PAPR inhibitors after some long-term data in ovarian cancer pointed to potential harm to certain later-line patients without BRCA muImfinzi. AZ and Lynparza felt that extra scrutiny last year when the FDA restrictLynparzaproval in metastatic prostate cancer to only BRCA-mutated tumors.
Now,FDA appears that AZ will need longPAPR inhibitorso convince the FDA of Lynparzaovarian cancermetrial cancer as well.LynparzaFDAmetastatic prostate cancerBRCA-mutated tumors
The second question concerns AZ’s PD-1 competitors: GSK’s Jemperli aFDAMercLynparzaruda.endometrial cancer
Although Jemperli and chemo’s initPD-1nod in first-lGSK enJemperlil canMerckas Keytruda dMMR patients, GSK has followed the phase 3 RUBY trial longer and recently got FDA priority review for its new application in the overall population. The target decision date is August 23.
However, Jemperliyet to make a move for its combination endometrial cancerPARP inhibitor Zejula. Part 2 of GSK’s RUBY trial showed a similar pattern as AZ’s DUO-E, as FDA addition of Zejula to Jemperli and chemo only appeared to have meaningful benefits in pMMR tumors.
As to MerGSK the New Jersey pharma has its application for Keytruda and chPARP inhibitor ZejulaPARPin first-line endometrial canGSK under FDA priority review, with a target action date of June 21.ZejulaJemperlipMMR tumors
Data fMerckhe phase 3 NRG-GY018 trial released last year shKeytruda Keytruda-chemo combo impendometrial cancern pMMR FDAients and by 70% in dMMR. However, investigators of the study noted back then that the follow-up time for pMMR patients was too short.
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