Despite last year's failed Acelera trial in the second/third-line setting, Roche continues to bet on its oral SERD giredestrant. The Pionera trial represents the fifth phase 3 to be initiated for the project, and will evaluate the giredestrant versus Faslodex, both in combination with investigators' choice CDK4/6 inhibitor, in approximately 1,050 ER-positive/HER2-negative breast cancer patients resistant to adjuvant endocrine therapy. The co-primary endpoints are progression-free survival in ESR1-mutation patients and all-comers. The company claims that the real potential lies in earlier settings than Acelera's, given that giredestrant responses are correlated to higher tumour ER-pathway activity, observed in early and pre-first-line breast cancer patients as well as in those with an ESR1 mutation. The initiation of Pionera places Roche as the leading company by number of ongoing phase 3 programmes in the SERD space. Giredestrant phase 3 programme in HR+/HER2- breast cancerTrialSettingRegimenNº of patientsPrimary endpointExpected readoutEveraFirst/second-line (prior CDK4/6i and ET in advanced or adjuvant setting)Combined with everolimus320PFS (ESR1m and ITT population)October 2024PerseveraFirst-lineCombined with palbociclib992PFSMarch 2025LideraAdjuvant (medium to high-risk Stage I-III)Monotherapy4,100IDFSDecember 2025PioneraFirst-line (resistance to ET)Combined with CDK4/6 inhibitor1,050PFS (ESR1m and FAS population)July 2026HerederaFirst-line maintenance after Phesgo inductionCombined with Phesgo812PFSAugust 2026Source: OncologyPipeline.
Despite last year's failed Acelera trial in the second/third-line setting, Roche continues to bet on its oral SERD giredestrant. The Pionera trial represents the fifth phase 3 to be initiated for the project, and will evaluate the giredestrant versus Faslodex, both in combination with investigators' choice CDK4/6 inhibitor, in approximately 1,050 ER-positive/HER2-negative breast cancer patients resistant to adjuvant endocrine therapy. The co-primary endpoints are progression-free survival in ESR1-mutation patients and all-comers. The company claims that the real potential lies in earlier settings than Acelera's, given that giredestrant responses are correlated to higher tumour ER-pathway activity, observed in early and pre-first-line breast cancer patients as well as in those with an ESR1 mutation. The initiation of Pionera places Roche as the leading company by number of ongoing phase 3 programmes in the SERD space.
Giredestrant phase 3 programme in HR+/HER2- breast cancer
| Trial | Setting | Regimen | Nº of patients | Primary endpoint | Expected readout |
|---|
| Evera | First/second-line (prior CDK4/6i and ET in advanced or adjuvant setting) | Combined with everolimus | 320 | PFS (ESR1m and ITT population) | October 2024 |
| Persevera | First-line | Combined with palbociclib | 992 | PFS | March 2025 |
| Lidera | Adjuvant (medium to high-risk Stage I-III) | Monotherapy | 4,100 | IDFS | December 2025 |
| Pionera | First-line (resistance to ET) | Combined with CDK4/6 inhibitor | 1,050 | PFS (ESR1m and FAS population) | July 2026 |
| Heredera | First-line maintenance after Phesgo induction | Combined with Phesgo | 812 | PFS | August 2026 |
