Based on DESTINY-Breast09 phase 3 trial results, which showed ENHERTU plus pertuzumab reduced the risk of disease progression or death by 44% versus THP with a median progression-free survival of greater than three years
Daiichi Sankyo and AstraZeneca’s supplemental Biologics License Application for ENHERTU in combination with pertuzumab has been accepted and granted Priority Review in the U.S. for the first-line treatment of adult patients with unresectable or metastatic HER2 positive breast cancer.
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
The U.S. Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA for ENHERTU plus pertuzumab based on data from the DESTINY-Breast09 phase 3 trial in July 2025. The Prescription Drug User Fee Act (PDUFA) date, the FDA target action date for their regulatory decision, is January 23, 2026.
The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of the FDA designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application.
The sBLA is based on data from DESTINY-Breast09 presented as a special late-breaking oral session at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting. In the trial, ENHERTU in combination with pertuzumab reduced the risk of disease progression or death by 44% versus taxane, trastuzumab and pertuzumab (THP) (hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.44-0.71; p<0.00001) as a first-line treatment for patients with HER2 positive metastatic breast cancer. Median progression-free survival (PFS) was 40.7 months (95% CI: 36.5-NC) with ENHERTU plus pertuzumab compared to 26.9 months (95% CI: 21.8-NC) for THP as assessed by blinded independent central review (BICR). The PFS benefit for ENHERTUplus pertuzumab versus THP was consistent across subgroups.
Confirmed objective response rate (ORR) with ENHERTU plus pertuzumab was 85.1% (95% CI: 81.2-88.5) versus 78.6% (95% CI: 74.1-82.5) with THP. There were 58 complete responses (CR) and 268 partial responses (PR) with ENHERTU plus pertuzumab compared to 33 CRs and 271 PRs with THP. Median duration of response (DOR) for ENHERTU plus pertuzumab exceeded three years (39.2 months) versus 26.4 months with THP.
“ENHERTU in combination with pertuzumab delayed disease progression for more than three years compared to around two years with current standard of care as a first-line treatment for patients with HER2 positive metastatic breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Receiving Priority Review moves us closer to offering ENHERTU to patients even earlier in the metastatic treatment pathway as a potential new first-line treatment option.”
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“The DESTINY-Breast09 trial showed that treating patients with HER2 positive metastatic breast cancer with ENHERTU in combination with pertuzumab until progression in the first-line setting produced a new landmark of more than 40 months for progression-free survival and nearly doubled the number of patients with no evidence of disease on imaging,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “This marks the first major evolution in treatment in this first-line setting in more than a decade – a setting where a strong response is crucial, as up to one third of patients may not receive second-line therapy.”
The safety profile of ENHERTU plus pertuzumab in DESTINY-Breast09 was consistent with the known profiles of each individual therapy with no new safety concerns identified. Grade 3 or higher treatment emergent adverse events (TEAEs) occurred in 54.9% of patients in the ENHERTU plus pertuzumab arm and 52.4% of patients in the THP arm. The most common grade 3 or higher TEAEs occurring in 5% or more of patients treated with ENHERTU plus pertuzumab were neutropenia (23.9%), hypokalemia (10.2%), anemia (8.4%), fatigue (7.9%), diarrhea (6.8%), thrombocytopenia (6.3%) and nausea (5.0%). Interstitial lung disease (ILD) or pneumonitis events occurred in 12.1% of patients treated with ENHERTU plus pertuzumab as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 [n=17; 4.5%] or grade 2 [n=27; 7.1%]). There were two grade 5 ILD events (0.5%) in the ENHERTU plus pertuzumab arm.
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ENHERTU is already approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
About DESTINY-Breast09
DESTINY-Breast09 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP as a first-line treatment in patients with HER2 positive metastatic breast cancer.
Patients were randomized 1:1:1 to receive either ENHERTU monotherapy with a pertuzumab matching placebo; ENHERTU in combination with pertuzumab; or THP. Randomization was stratified by prior treatment, hormone receptor (HR) status and PIK3CA mutation status.
The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the ENHERTU monotherapy and ENHERTU combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, ORR, DOR, pharmacokinetics and safety. The investigational arm assessing ENHERTUmonotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.
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Source – businesswire
