Evolution of ADCs… Enhertu prolongs OS in solid tumors

Additional data released on its efficacy in HER2-low expression breast cancer… meets primary endpoint

Shows effect in multiple solid tumors, including biliary tract and head and neck cancers that progressed following prior therapy

The antibody-drug conjugate (ADC) anticancer drug Enhertu has demonstrated further efficacy across multiple solid tumors, including HER2-low breast, biliary tract, and head and neck cancers.

 

With the clinical results, the company secured momentum to add more solid tumors to Enhertu’s already established breast, gastric, and non-small cell lung cancer indications.

 

Enhertu is Daiichi Sankyo and AstraZeneca’s ADC anticancer drug.

 

Enhertu is a next-generation ADC that combines a monoclonal antibody with the same structure as trastuzumab, which binds to a specific target receptor overexpressed on the surface of cancer cells, and a topoisomerase I inhibitor payload with a tumor-selective cleavable linker, a novel and highly potent mechanism of action.

 

Enhertu has been recognized for overcoming the limitations of existing therapies and is effective across solid tumors, not for just a single indication.

 

Enhertumakes strides in HER2-low breast cancer According to industry sources on the 3rd, additional clinical data on Enhertu was presented at the 2024 American Society of Clinical Oncology Annual Meeting (ASCO 2024) that is being held in Chicago, U.S.

 

On the 2nd, results from the DESTINY-BREAST06 trial, which demonstrated the additional benefit of Enhertu in HER2 low-expression breast cancer, were presented at ASCO 2024 (Source: ASCO 2024 lecture capture)

The clinical trial evaluated the efficacy and safety of Enhertu in patients with HR-positive, HER2-low or HER2-ultralow advanced or metastatic breast cancer whose disease progressed following one or more lines of endocrine therapy.

 

 The HER2-low arm included immunohistochemistry (IHC) 1 or 2/fluorescent in situ hybridization (ISH) negative patients, and the ultra-low-expression arm included IHC 0 patients.

 

The participants were randomly assigned 1:1 to receive either Enhertu or the investigator’s choice of chemotherapy (capecitabine, nab-paclitaxel, or paclitaxel).

 

The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by a blinded independent review committee (BICR).

 

Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), OS in the HER2-low patient population, and OS in the overall trial population.

 

Other exploratory endpoints included objective response rate (ORR) and safety.

 

Study results showed that the median PFS with Enthertu was 13.2 months in the HER2-low cancer patient population, which was longer than the 8.1 months in the chemotherapy arm.

 

The difference was also evident in the HER2-ultralow patient population.

 

PFS was 13.2 months in the Enhertu arm versus 8.3 months in the chemotherapy arm.

 

In patients with HER2-low expression, the confirmed objective response rate (ORR) was 56.5% for Enhertu versus 32.2% with chemotherapy, and in patients with HER2-ultralow expression, the confirmed ORR was 61.8% versus 26.3%, respectively.

 

The OS data were immature.

 

The researchers concluded that "Enhertu could become a new standard of care for patients with hormone-positive breast cancer following endocrine therapy in the metastatic setting.” Demonstrated prolonged survival in head and neck, biliary, and pancreatic cancers Enhertu has also demonstrated survival benefits in head and neck, biliary tract, and pancreatic cancers.

 

The DESTINY-Pantumor02 trial verified Enhertu’s efficacy in patients with previously treated pancreatic, ovarian, cervical, bladder, biliary, endometrial, or other tumors.

 

Based on the trial results, Enhertu’s indication was expanded across HER2 solid tumors for which there are no treatment alternatives.

 

The study presented at ASCO 2024 is a follow-up to DESTINY-Pantumor02 in head and neck, biliary tract, and pancreatic cancers.

 

The Phase II study evaluated the efficacy of Enhertu in patients with locally advanced, metastatic HER2-positive head and neck cancer following systemic therapy.

 

The primary endpoint was ORR; secondary endpoints included DOR, PFS, disease control rate (DCR), and safety; and exploratory endpoints included efficacy outcomes by HER2 expression.

 

At the time of data cutoff (June 2023), 24 patients with head and neck cancer were evaluated, resulting in an ORR of 41.7% for Enhertu.

 

Median DOR was 22.1 months and the median PFS was 12.4 months.

 

Safety was consistent with known safety profiles.

 

In the DESTINY-Pantumor02 subgroup analysis, Enhertu also showed promise in pancreatic and biliary cancers.

 

In this study, Enhertu achieved a primary endpoint ORR of 22.0% and a median PFS of 4.6 months.

 

These results are paving the way for Enhertu to expand its indication across all solid tumors with HER2 expression.