First Head-to-Head Phase 3 Trial of ENHERTU Launched in First-Line HER2-Mutant Metastatic Non-Small Cell Lung Cancer

December 26, 2021 /BioValleyBIOON/ -- Daiichi Sankyo recently announced the global Phase 3Clinical TrialDESTINY-Lung04 has dosed the first patient. The trial is being conducted in previously untreated patients with HER2-mutated unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) and is evaluating the efficacy and safety of Enhertu (trastuzumab deruxtecan) for first-line treatment.

Enhertu is a HER2-targeted antibody-drug conjugate (ADC)., by Daiichi Sankyo andAstraZenecaCo-development. DESTINY-Lung04 is the first head-to-head trial of Enhertu in NSCLC,Compare Enhertu as a first-line treatment regimen with the standard-of-care regimen (platinum-pemetrexed doublet chemotherapy + Keytruda)., to evaluate the efficacy of treating patients with unresectable, locally advanced or metastatic non-squamous NSCLC carrying HER2 exon 19 or 20 mutations.

Lung cancer is the leading cause of cancer death, accounting for approximately one-fifth of global cancer deaths. Among lung cancer cases, 80%-85% are classified as non-small cell lung cancer (NSCLC). HER2 is a tyrosine kinase receptor, a type of growth-promoting protein, expressed in variousTumorSurface, including lung cancer,Breast Cancer, gastric cancer, and colorectal cancer. Currently, there are no drugs specifically approved for the treatment of HER2-mutant NSCLC. HER2 mutations affect approximately 2%-4% of non-squamous NSCLC patients. The standard of care for first-line metastatic treatment in patients with HER2-mutant NSCLC is PD-1 or PD-L1 immunotherapy (with or without platinum-based chemotherapy). Although these treatments can improve patient survival, approximately 40%-60% ofTumorFor this type of initial treatment failure, disease progression occurs, thus there is an urgent need for additional treatment methods.

Senior Vice President of Daiichi SankyoTumorStudy lead Gilles Gallant, Ph.D., said, "Data from the DESTINY-Lung01 trial show that Enhertu demonstrated strong and durable responses in patients with HER2-mutated metastatic NSCLC previously treated. Based on these impressive findings, we are conducting the DESTINY-Lung04 study to evaluate the potential of Enhertu as an earlier first-line treatment for this patient population."

At the end of January 2021, Daiichi Sankyo and AstraZeneca participated in the 21st World Conference on Lung Cancer (WCLC) hosted online by the International Association for the Study of Lung Cancer in 2020.MeetingPublished DESTINY-Lung01 Phase II in ChinaClinical TrialNew Data from the Non-Small Cell Lung Cancer (NSCLC) Cohort. Interim analysis data indicate that Enhertu demonstrates highly promising and durable anti-tumor activity in patients with HER2-overexpressing metastatic NSCLC.TumorActivity.

In the DESTINY-Lung01 Phase II trial Cohort 1, patients with HER2-overexpressing (defined as IHC3+ or IHC2+) metastatic NSCLC who had previously received multiple treatment regimens (chemotherapy, molecular targeted therapy, immunotherapy) were enrolled (n=49). The median number of prior treatment regimens was 3, with the majority having received platinum-based chemotherapy (91.8%) or immunotherapy (73.5%). In the study, patients (n=49) were treated with Enhertu (6.4mg/kg), with a median treatment duration of 18 weeks. As of the data cutoff on May 30, 2020, 22% of patients were still receiving Enhertu treatment.

The results presented at the meeting showed that, as assessed by independent central review, HER2-overexpressing metastatic NSCLC patients previously treated with multiple regimens achieved responses after receiving Enhertu (6.4mg/kg).The confirmed overall response rate (ORR) was 24.5%, disease control rate (DCR) was 69.4%, median progression-free survival (PFS) was 5.4 months. After a median follow-up of 6.1 months, the estimated median duration of response (DOR) was 6.0 months, and the median overall survival (OS) was 11.3 months.

Interim data from the DESTINY-Lung01 study HER2-mutated (HER2m) metastatic NSCLC cohort (n=42) were previously presented at the 2020 American Society of Clinical Oncology (ASCO) virtual meeting and re-presented at WCLC. The results showed that Enhertu also achieved clinically meaningful outcomes in patients with HER2m metastatic NSCLC.TumorReaction.

In recent years, the introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes for patients with advanced NSCLC. However, new treatment options are needed for those who are ineligible for effective therapies or whose cancer continues to progress. Currently, no HER2-directed therapies are approved for the treatment of NSCLC with HER2 alterations.

May 2020, United StatesFDAGrant Enhertu Breakthrough Therapy Designation (BTD) for the treatment of patients whose disease has progressed during or after receiving platinum-based chemotherapy.TumorPatients with metastatic NSCLC harboring HER2 mutations in China. If approved, Enhertu has the potential to become the first HER2-directed therapy approved for the treatment of NSCLC.

In March 2019, AstraZeneca and Daiichi Sankyo reached a $6.9 billion immunotherapy agreement.TumorThrough academic collaboration, Enhertu will be co-developed globally to treat cancer patients with various HER2 expression levels or HER2 mutations, including gastric cancer, colorectal cancer, lung cancer, and HER2-low breast cancer. Daiichi Sankyo retains exclusive rights in the Japanese market and will fully oversee manufacturing and supply.

To date, Enhertu has been approved for the treatment of two types of cancer: (1) for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received at least two HER2-based regimens. (2) for the treatment of patients with HER2-positive unresectable advanced or recurrent gastric cancer.

The industry has high expectations for the commercial prospects of Enhertu. EvaluatePharma, a pharmaceutical market research firm, previously predicted that Enhertu's sales in 2024 are expected to reach $2.5 billion. Some industry analysts also forecast that Enhertu’s annual sales peak will exceed $4 billion. (Bioon.com)

Source of Original Text:DESTINY-Lung04 Phase 3 Trial of ENHERTU Initiated in Patients with Previously Untreated HER2 Mutant Metastatic Non-Small Cell Lung Cancer