Positive findings from an interim analysis of the ongoing DESTINY-PanTumor02 Phase II trial, evaluating ENHERTU in a wide range of HER2-expressing solid tumors, were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. This trial marks the first global study of ENHERTU's tumor-agnostic applications across various HER2-expressing solid tumors, excluding breast, gastric, colorectal, and non-small cell lung cancers.
The trial enrolled 267 patients with advanced or metastatic HER2-expressing tumors that had worsened after previous treatments or had no available treatment options. The patients received at least one dose of ENHERTU, a HER2-directed antibody-drug conjugate developed by AstraZeneca and Daiichi Sankyo.
In the trial, previously treated patients with HER2-expressing advanced solid tumors showed a confirmed objective response rate (ORR) of 37.1%, as assessed by the investigator in an interim analysis. Patients with the highest level of HER2 expression (IHC 3+) demonstrated a higher response rate, with a confirmed ORR of 61.3% based on central testing. The trial also observed a complete response (CR) in 15 patients, a partial response (PR) in 84 patients, and stable disease in 123 patients, resulting in a disease control rate (DCR) of 68.2% in the overall trial population.
Nearly half of the patients (49.6%) who achieved a response remained in response for one year. The median duration of response (DoR) was 11.8 months in the overall trial population and 22.1 months in patients with IHC 3+ expression.
The safety profile of ENHERTU was consistent with previous clinical trials, with no new safety concerns identified. The most common Grade 3 or higher treatment-related adverse events included neutropenia, anemia, fatigue, and thrombocytopenia. However, 7.5% of patients experienced interstitial lung disease (ILD) or pneumonitis related to ENHERTU treatment, with the majority being low-grade.
These positive interim results demonstrate the potential of ENHERTU in providing clinically meaningful responses and durable benefits across a broad range of HER2-expressing solid tumors, addressing an unmet need in this patient population. Further investigation and follow-up will continue to evaluate the efficacy and safety of ENHERTU in these indications.
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KOL insights
“These results advance our clinical understanding of HER2 expression; reaffirm HER2 as an actionable biomarker across a broad range of tumor types; and show that T-DXd could potentially provide a new treatment option for patients with the advanced disease across these tumors, especially in patients with HER2 IHC 3+ or 2+ expression” –Expert Opinion.
“This study provides data for an unmet need for patients who have exhausted standard therapeutic options with tumors that overexpress HER2 for which no drug is yet approved. While additional follow-up is needed, there is robust activity across multiple HER2-expressing tumors, with [an] over 50% response rate in those with the highest levels of HER2 expression coupled with an encouraging safety profile. [T-DXd] could provide a new treatment option for these patients”–Expert Opinion.
Conclusion
Upon examining the results of the trial based on HER2 expression levels, patients were categorized into cohorts of IHC 2+ and IHC 3+. The outcomes favored the latter group, indicating better responses. Additionally, apart from pancreatic cancer, the response rates were consistently impressive across different tumor types.
Although HER2 is expressed in various types of tumors, there are currently no approved therapies targeting HER2 for many cancer types, particularly those that are challenging to treat. ENHERTU has gained approval from the US FDA for HER2-positive breast cancer, HER2-positive gastric cancer, and lung cancers with HER2 mutations.
This study addresses an unmet need for patients who have exhausted standard treatment options and have tumors overexpressing HER2, for which no approved drugs are available. While further follow-up is necessary, the data demonstrates significant activity in multiple HER2-expressing tumors. Suggesting ENHERTU has the potential to offer a new treatment alternative for these patients
