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AZ and Daiichi Sankyo’s third Breakthrough Therapy Designation for Enhertu

May 18, 2020: “AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan) has been granted Breakthrough Therapy Designation (BTD) in the US for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2 mutation and with disease progression on or after platinum-based therapy.

NSCLC is the most common type of lung cancer, and prognosis is particularly poor for patients with metastatic disease as only about 6-10% will be alive five years after diagnosis.

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Approximately 2-4% of patients with NSCLC have a HER2 mutation.

The Food and Drug Administration (FDA)’s BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need.

The new medicine needs to have shown encouraging early clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.

José Baselga, Executive Vice President, R&D Oncology, said: “Today’s news is very welcome as we continue to evaluate the potential of Enhertu to help patients with this devastating type of lung cancer.

Targeted treatments and immunotherapies are demonstrating tremendous advancements, but there remains an unmet medical need for patients with HER2 mutations who are not benefiting from such therapies or for those whose cancer continues to progress.”

Gilles Gallant, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo, said: “We are encouraged by the promising evidence of activity seen with Enhertu in patients with advanced lung cancer and a HER2 mutation.

We look forward to working closely with the FDA on the potential for Enhertu to become the first HER2-directed therapy approved for non-small cell lung cancer.”

The FDA granted BTD based on data from the ongoing Phase II DESTINY-Lung01 trial currently testing Enhertu, a HER2-directed antibody drug conjugate (ADC),in patients with HER2-mutant (HER2m) metastatic NSCLC, and data from the Phase I trial published in Cancer Discovery.

An interim analysis from DESTINY-Lung01 will be presented during the 2020 American Society of Clinical Oncology ASCO20 Virtual Scientific Program, 29 to 31 May 2020.

The overall safety and tolerability profile of Enhertu in the ongoing DESTINY-Lung01 trial is consistent with that seen in the Phase I trial.

The most common adverse events to date (n=42) are gastrointestinal and haematological including nausea, alopecia, anaemia, decreased appetite and decreased neutrophil count.

There have been five cases of drug-related interstitial lung disease (ILD) and pneumonitis in patients with HER2m NSCLC, all of which were Grade 2. There have been no ILD-related deaths.

This is the third BTD granted for Enhertu in the US. Last week, Enhertu received BTD in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received two or more prior regimens including trastuzumab. 

Enhertu received BTD in 2017 for HER2-positive metastatic breast cancer and received approval in December 2019.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours.

In some tumours, HER2 overexpression is associated with a specific HER2 gene alteration known as amplification and is often associated with aggressive disease and poorer prognosis.

Other HER2 gene alterations (called HER2 mutations) have been identified in NSCLC, specifically adenocarcinomas, as distinct molecular targets.

 Approximately 2-4% of patients with NSCLC have HER2 mutations, which have been independently associated with cancer cell growth and poor prognosis.


Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.

In the US, it is estimated that 228,820 new cases of lung cancer will be diagnosed in 2020 and more than 135,000 people will die from the disease.

Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC. Within NSCLC, patients are classified as squamous, representing 25-30% of patients, or non-squamous, the most common type representing approximately 70-75% of NSCLC patients.

Stage IV is the most advanced form of lung cancer and is often referred to as metastatic disease.

For these patients with metastatic disease, prognosis is particularly poor, as only 6-10% will be alive five years after diagnosis.

 The introduction of targeted therapies and checkpoint inhibitors in recent years has improved outcomes for patients with advanced NSCLC; however, new approaches are needed for those who are not eligible for available treatments, or whose cancer continues to progress.

Currently, no medicine is specifically approved for patients with HER2m NSCLC.


DESTINY-Lung01 is a global, Phase II, open-label, multicentre, two-cohort trial assessing the safety and efficacy of Enhertu in 170 patients with HER2m (n=90) or HER2-overexpressing, defined as IHC 3+ or IHC 2+, (n=80) unresectable and metastatic non-squamous NSCLC whose cancer has progressed after one or more systemic therapies (including chemotherapy, molecular targeted therapy or immunotherapy).

The primary endpoint is ORR. Key secondary endpoints include duration of response, disease control rate, progression-free survival and overall survival.

Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Enhertu is approved in the US and Japan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the DESTINY-Breast01 trial.”

For More News:

AstraZeneca’s US Breakthrough Therapy Designation for Enhertu

Phase II DESTINY-Gastric01 trial of Enhertu (trastuzumab deruxtecan) versus chemotherapy met primary endpoint

Daiichi Sankyo ENHERTU® is Now Available in the U.S. for the HER2 Positive Unresectable or Metastatic Breast Cancer Following Two or More Prior Anti-HER2-Based Regimens


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