Positive Phase 2 Data Show Enhertu Significantly Improves Survival in Patients with HER2-Expressing Advanced Solid Tumors

▎Edited by the WuXi AppTec content team

Recently, AstraZeneca and Daiichi Sankyo announced positive results from the Phase 2 clinical trial DESTINY-PanTumor02. The results showedHER2-targeted antibody-drug conjugate (ADC) Enhertu continues to demonstrate clinically meaningful and sustained efficacy, bringing significant survival benefits to patients with previously treated, HER2-overexpressing advanced solid tumors.. These results include the first public disclosure of progression-free survival (PFS) and overall survival (OS) data from the trial. The detailed study data were orally presented at the 2023 European Society for Medical Oncology (ESMO) Congress and simultaneously published in the Journal of Clinical Oncology.

HER2 is a tyrosine kinase receptor pro-growth protein expressed on the surface of various types of tumors, including breast cancer, gastric cancer, lung cancer, and colorectal cancer.Overexpression of HER2 protein may be the result of HER2 gene amplification or activating mutations, and is often associated with cancer aggressiveness and poor prognosis.HER2 overexpression can be found in various types of metastatic solid tumors, with a proportion of 1-28%. HER2 overexpression is observed in approximately 5% of colorectal cancer patients.

Enhertu (trastuzumab deruxtecan) is an ADC therapy jointly developed by AstraZeneca and Daiichi Sankyo.It is designed using Daiichi Sankyo's proprietary DXd ADC technology platform, consisting of a humanized monoclonal antibody targeting HER2, linked via a cleavable tetrapeptide linker to a topoisomerase I inhibitor payload.。

In the primary analysis of this trial, as assessed by the investigators,Enhertu Demonstrates a Confirmed Objective Response Rate (ORR) of 37.1% in Patients (n=267) with HER2-Overexpressing Advanced Solid Tumors (Including Biliary Tract, Bladder, Cervical, Endometrial, Ovarian, Pancreatic, or Other Cancers) Previously Treated（95% CI：31.3-43.2）。Median Duration of Response (DOR) was 11.3 months（95% CI：9.6-17.8），The median PFS was 6.9 months (95% CI: 5.6-8.0), and the median OS was 13.4 months.(95% CI: 11.9-15.5). As of the data cutoff date of June 8, 2023, the median follow-up time was 12.75 months.

In an exploratory analysis of 75 patients with HER2-positive (IHC 3+),Enhertu Treatment Confirmed ORR of 61.3%（95% CI：49.4-72.4）。The median DOR for HER2-positive (IHC 3+) patients was 22.1 months.（95% CI：9.6-NR），Median PFS was 11.9 months（95% CI：8.2-13.0），Median OS was 21.1 months(95% CI: 15.3-29.6). These clinically meaningful results confirm the interim findings from the DESTINY-PanTumor02 study presented earlier this year at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The safety observed in the DESTINY-PanTumor02 trial was consistent with previous clinical trials of Enhertu, with no new safety issues identified.40.8% of patients experienced treatment-related adverse events (TEAEs) of Grade 3 or higher. The most common Grade 3 or higher TEAEs, occurring in ≥5% of patients, included: neutropenia (19.1%), anemia (10.9%), fatigue (7.1%), and thrombocytopenia (5.6%). In the DESTINY-PanTumor02 trial, as determined by an independent review committee, 10.5% of patients (n=28) developed any grade of interstitial lung disease (ILD) or pneumonia related to Enhertu treatment. Most ILD or pneumonia events were low-grade (Grade 1 [n=7; 2.6%] or Grade 2 [n=17; 6.4%]), with one Grade 3 (0.4%), zero Grade 4 (0%), and three Grade 5 (1.1%) events observed during the trial.