61.9% of patients with HER2-mutant metastatic non-small cell lung cancer treated with ENHERTU achieved a tumor response

Breakthrough Therapy Designation recently granted in the US for ENHERTU in this setting

WILMINGTON, DE, USA I May 29, 2020 I Results from the ongoing Phase II DESTINY-Lung01 trial showed AstraZeneca and Daiichi Sankyo Company, Limited’s (Daiichi Sankyo) ENHERTU® (fam-trastuzumab deruxtecan-nxki) achieved a clinically meaningful tumor response in patients with HER2-mutant (HER2m) unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC) whose disease had progressed following one or more systemic therapies.

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths globally, with 80-85% classified as NSCLC. There are currently no medicines approved specifically for the treatment of HER2m NSCLC, which affects approximately 2-4% of patients with NSCLC.

The primary endpoint of confirmed objective response rate (ORR), assessed by independent central review, was 61.9% for patients treated with ENHERTU monotherapy (6.4mg/kg). Patients achieved a disease control rate (DCR) of 90.5% with an estimated median progression-free survival (PFS) of 14.0 months. Median duration of response (DoR) and overall survival (OS) had not yet been reached at the time of data cut-off.

Egbert F. Smit, Professor, MD, Department of Thoracic Oncology at the Netherlands Cancer Institute, Amsterdam, Netherlands and principal investigator in the Phase II DESTINY-Lung01 trial, said: “While there have been important advances in the treatment of lung cancer over the past decade, there are still patients whose tumors continue to progress despite treatment with newer targeted agents or immunotherapies. Understanding additional molecular targets for treatment, such as HER2, is critical to advancing treatment options for these patients and the results seen in the DESTINY-Lung01 trial are very encouraging.”

José Baselga, Executive Vice President, R&D Oncology, said: “The results seen with ENHERTU in patients with metastatic HER2-mutant non-small cell lung cancer are very exciting and highlight the role ENHERTU may have as a new treatment option for patients facing a devastating prognosis. Further, the results demonstrate the potential of ENHERTU to treat another tumor type among patients with extremely high unmet need.”

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: “While the role of anti-HER2 treatment is well-established in breast and gastric cancers, there are no HER2-directed therapies specifically approved for lung cancer. These results validate HER2 mutations as actionable targets in lung cancer and offer further evidence that ENHERTU has the potential to transform outcomes for patients across a spectrum of HER2-targetable cancers.”

Summary of results

  HER2m Total Evaluable (n=42)i
Confirmed ORR (%) (95% CI)ii, iii 61.9 (45.6-76.4)
CR (%) 2.4
PR (%) 59.5
SD (%) 28.6
DCR (%) (95% CI)iv 90.5 (77.4-97.3)
Median DoR (months) (95% CI) NE (5.3-NE)
Median PFS (months) (95% CI) 14.0 (6.4-14.0)
Median OS (months) (95% CI) NE (11.8 – NE)

CI, confidence interval; CR, complete response; PR, partial response; SD, stable disease; NE, not estimable
i ENHERTU 6.4 mg/kg
ii As assessed by independent central review.
iii ORR is (CR + PR)
iv DCR is (CR+PR+SD)

Patients were treated with a median of two prior therapies (1-6) with most receiving platinum-based chemotherapy (90.5%) and anti-PD-1 or PD-L1 treatment (54.8%). Median treatment duration was 7.76 months (0.7-14.3) with a median duration of follow-up of 8.0 months (1.4-14.2). As of data cut-off on November 25, 2019, 45.2% of patients with HER2m NSCLC remained on treatment.

The overall safety and tolerability profile of ENHERTU in DESTINY-Lung01 was consistent with that seen in the Phase I lung cancer trial and previously reported ENHERTU trials. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (26.2%) and anemia (16.7%). There were five cases (11.9%) of confirmed treatment-related interstitial lung disease (ILD) and pneumonitis as determined by independent review. All ILD and pneumonitis cases were Grade 2. One Grade 1 ILD is still undergoing adjudication.

Results from the DESTINY-Lung01 trial were presented today during the 2020 American Society of Clinical Oncology (ASCO20) Virtual Scientific Program on May 29-31, 2020. Several other presentations featured during the ASCO20 Virtual Scientific Program will showcase AstraZeneca’s leadership in lung cancer across early and late-stage disease and reinforce the Company’s biomarker-driven approach.

ENHERTU was recently granted Breakthrough Therapy Designation in the US for the treatment of patients with metastatic NSCLC whose tumors have a HER2 mutation and whose disease progressed on or after platinum-based therapy. ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who received two or more prior anti-HER2-based regimens based on the DESTINY-Breast01 trial. ENHERTU has not been approved in the United States for non-small cell lung cancer.

FDA-Approved Indication for ENHERTU
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated 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 in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see accompanying full Prescribing Information, including Boxed WARNING, and Medication Guide.

NOTES TO EDITORS

HER2
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers. In some tumors, 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.

NSCLC
Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths globally. 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 SCLC, 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 HER2-mutant NSCLC.

DESTINY-Lung01
DESTINY-Lung01 is a global, Phase II, open-label, multicenter, two-cohort trial testing the safety and efficacy of ENHERTU in 170 patients with HER2mor HER2-overexpressing, defined as IHC3+ or IHC2+, unresectable and/or metastatic non-squamous NSCLC. Patients had progressed after one or more systemic therapies including chemotherapy, molecular targeted therapy or immunotherapy. The primary endpoint is confirmed ORR by independent central review. ORR, or tumor response rate, represents the percentage of patient whose disease decreased and/or disappears. Key secondary endpoints include DoR, DCR, PFS and OS.

ENHERTU
ENHERTU (fam-trastuzumab deruxtecan-nxki in the US only) is a HER2-directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program 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 Clinical Development
A comprehensive development program is underway globally with six registrational trials evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2-driven cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize ENHERTU worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory and Immunology. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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SOURCE: AstraZeneca