Tokyo - Results from the primary analysis of the DESTINY-Lung02 phase 2 trial showed ENHERTU (trastuzumab deruxtecan) continued to demonstrate strong and durable tumor responses in previously treated patients with HER2 mutant unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC).

These results, along with the first report on progression-free survival (PFS) and overall survival (OS), were presented today (MA 13.10) at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC23) and simultaneously published in the Journal of Clinical Oncology.

ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo (TSE:4568) and AstraZeneca (LSE/STO/Nasdaq: AZN). At the primary analysis, a confirmed objective response rate (ORR) of 49.0% (95% confidence interval [CI]: 39.0-59.1) in the 5.4 mg/kg arm and 56.0% (95% CI: 41.3-70.0) in the 6.4 mg/kg arm was observed as assessed by blinded independent central review (BICR). One (1.0%) complete response (CR) and 49 (48.0%) partial responses (PR) were observed in the 5.4 mg/kg arm and two (4.0%) CRs and 26 (52.0%) PRs were observed in the 6.4 mg/kg arm. The disease control rate (DCR) was 93.1% (95% CI: 86.4-97.2) at the 5.4 mg/kg dose and 92.0% (95% CI: 80.8-97.8) at the 6.4 mg/kg dose. The median duration of response (DoR) was 16.8 months (95% CI: 6.4-not estimable [NE]) in the 5.4 mg/kg arm and was not reached in the 6.4 mg/kg arm (95% CI: 8.3-NE).

Median PFS as assessed by BICR was 9.9 months (95% CI: 7.4-NE) in the 5.4 mg/kg arm and 15.4 months (95% CI: 8.3-NE) in the 6.4 mg/kg arm. Median OS was 19.5 months (95% CI: 13.6-NE) in the 5.4 mg/kg arm and not reached (95% CI: 12.1-NE) in the 6.4 mg/kg arm. Median follow-up was 11.5 months in the 5.4 mg/kg arm (n=102) and 11.8 months in the 6.4 mg/kg arm (n=50) at time of data cutoff of December 23, 2022. The primary results from DESTINY-Lung02 demonstrate that ENHERTU continues to show strong and durable tumor responses for patients treated at either dose, said Pasi A. Janne, MD, PhD, Director, Lowe Center for Thoracic Oncology and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute. The favorable safety profile seen at the 5.4 mg/kg dose continues to support the use of ENHERTU in the treatment of patients with HER2 mutant non-small cell lung cancer, a particularly aggressive form of the disease where patients face a poor prognosis and have historically had few options.

In DESTINY-Lung02, a favorable safety profile was observed in patients treated with ENHERTU 5.4 mg/kg with no new safety signals identified at either dose. Grade 3 or higher treatment-related treatment emergent adverse events (TEAEs) were lower with ENHERTU 5.4 mg/kg versus 6.4 mg/kg. Grade 3 or higher treatment-related TEAEs occurred in 38.6% and 58.0% of all patients receiving ENHERTU 5.4 mg/kg or 6.4 mg/kg, respectively. The most common grade 3 or higher TEAEs were neutropenia (18.8% [5.4 mg/kg]; 36.0% [6.4 mg/kg]) and anemia (10.9% [5.4 mg/kg]; 16.0% [6.4 mg/kg]). There were 27 cases of treatmentrelated interstitial lung disease (ILD) or pneumonitis reported as determined by an independent adjudication committee (12.9% [n=13/101] in the 5.4 mg/kg arm; 28.0% [n=14/50] in the 6.4 mg/kg arm). In the 5.4 mg/kg arm, the majority of ILD cases were low grade (grade 1 or 2 [10.9%; four grade 1 and seven grade 2 events]) with one grade 3 event, zero grade 4 events and one grade 5 event observed. In the 6.4 mg/kg arm, the majority of ILD cases were low grade (grade 1 or 2 [26.0%; four grade 1 and nine grade 2 events]) with zero grade 3 events, zero grade 4 events and one grade 5 event observed.

The disease control achieved by more than 90% of patients with previously treated HER2 mutant non-small cell lung cancer in the primary analysis of DESTINY-Lung02 reinforces the efficacy we have already seen with ENHERTU in this hard-to-treat disease, said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. These results, along with encouraging progression-free survival and overall survival findings reported for the first time, demonstrate the potential role of ENHERTU as an important treatment option for this patient population

These results from DESTINY-Lung02 highlight that HER2 is an actionable target in lung cancer and reinforce the importance of testing for predictive biomarkers, including HER2 alterations in lung cancer, at the time of diagnosis to accurately identify patients who may be able to benefit from a targeted treatment, said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. The data also reaffirm our belief in ENHERTU as a potential new targeted treatment option for patients who have historically had limited options.

Patients in the DESTINY-Lung02 trial received a median of two prior cancer therapies in each ENHERTU arm (5.4 mg/kg: range 1-12; 6.4 mg/kg: range 1-7). HER2 mutations were primarily in the kinase domain (5.4 mg/kg: 97.1%; 6.4 mg/kg: 100%). Baseline central nervous system metastases were present in 34.3% of patients in the 5.4 mg/kg arm and 44.0% of patients in the 6.4 mg/kg arm. Median follow-up was 11.5 months (range 1.1-20.6) in the 5.4 mg/kg arm and 11.8 months (range 0.6-21.0) in the 6.4 mg/kg arm.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.

About Daiichi Sankyo

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need.

Contact:

Koji Ogiwara

Email: ogiwara.koji.ay@daiichisankyo.co.jp

Tel: +81 3 6225 1126

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