April 19, 2022: “AstraZeneca and Daiichi Sankyo have received notification of acceptance of the supplemental Biologics License Applicationof Enhertu (trastuzumab deruxtecan) for the treatment of adult patients in the US with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2(ERBB2) mutation and who have received a prior systemic therapy.
The application has also been granted Priority Review.
Enhertu is a HER2–directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.
The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is during the third quarter of 2022.
The Priority Review follows Breakthrough Therapy Designation granted by the FDA for Enhertu in this cancer type in May 2020.
Lung cancer is the second most common form of cancer globally, with more than two million new cases diagnosed in 2020.
For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.
There are currently no HER2-directed therapies approved specifically for the treatment of HER2–mutant NSCLC, which occurs in approximately 2-4% of patients with non-squamous NSCLC.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The DESTINY-Lung01 trial confirmed the HER2 mutation as an actionable biomarker in non-small cell lung cancer.
If approved, Enhertu has the potential to become a new standard treatment in this patient population, offering a much-needed option for patients with HER2-mutant metastatic non-small cell lung cancer who currently have no targeted treatment options.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The results of DESTINY-Lung01 showed that Enhertu is the first HER2-directed therapy to demonstrate a strong and robust tumour response in more than half of patients with previously treated HER2-mutant metastatic non-small cell lung cancer.
Seeking approval in the US for a third tumour type in three years further demonstrates the significant potential of Enhertu in treating multiple HER2-targetable cancers.”
The sBLA is based on data from the registrational DESTINY-Lung01 Phase II trial published in The New England Journal of Medicine, and is supported by the Phase I trial (DS8201-A-J101) published in Cancer Discovery.
Primary results from previously-treated patients with HER2-mutations (cohort 2) of DESTINY-Lung01 demonstrated a confirmed objective response rate (ORR) of 54.9% (95% confidence interval [CI]: 44.2-65.4) in patients treated with Enhertu (6.4mg/kg) as assessed by independent central review (ICR).
One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were observed.
A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in tumour size observed in most patients. After a median follow-up of 13.1 months, the median duration of response (DoR) for Enhertu was 9.3 months.
The median progression-free survival (PFS) was 8.2 months and the median overall survival (OS) was 17.8 months.
The safety profile of the most common adverse events with Enhertu in DESTINY-Lung01 was consistent with previous clinical trials with no new safety concerns identified.
Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.”
