'Datroway' launches in Korea…breast cancer ADC

The market competition intensifies

Approved as a treatment for HR+/HER2- metastatic breast cancer

Improved major evaluation index…potential as a treatment for triple-negative breast cancer (TNBC)

A Trop-2-directed antibody-drug conjugate (ADC), Datroway, obtained domestic approval, introducing a new treatment option to breast cancer. Based on clinical results, which show improved progression-free survival (PFS) compared with existing cytotoxic anticancer drugs. Attention is drawn to the possibility of expansion of the TROP2 ADC-based treatment strategy to triple-negative breast cancer (TNBC) beyond HR+/HER2- breast cancer.

ADC anticancer drug 'Datroway'

According to industry sources on the 11th, the Ministry of Food and Drug Safety (MFDS) approved Datroway (datopotamab deruxtecan), developed by AstraZeneca and Daiichi Sankyo, as a breast cancer treatment.

The specific indication is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

AstraZeneca paid $1 billion (approx. KRW 1 trillion) in upfront fees alone to secure the development rights for Datroway from Daiichi Sankyo in 2020. The total contract value, including development and commercialization milestones, amounts to $6 billion (approx. KRW 7 trillion).

Datroway's target TROP2 is rapidly emerging as a core target in global ADC development.

The TROP2 protein is known to be overexpressed in various cancer types, including breast cancer and non-small cell lung cancer (NSCLC). Datroway's mechanism of action involves binding to this protein and delivering cytotoxic drugs directly inside cancer cells to induce apoptosis. It is designed to maintain the efficacy of conventional cytotoxic chemotherapy while reducing damage to healthy cells.

The basis for this approval is the Phase 3 TROPION-Breast01 study. This study was conducted on 732 patients with unresectable or metastatic HR-positive, HER2-negative breast cancer.

Patients were randomized 1:1 into the Datroway group (365 patients) and the physician's choice of chemotherapy (TPC) group (367 patients).

Datroway was administered intravenously at a dose of 6 mg/kg every three weeks, while the control group received an investigator's choice of chemotherapy among eribulin, capecitabine, vinorelbine, or gemcitabine.

Primary endpoints included progression-free survival (PFS) and overall survival (OS) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 criteria. Objective response rate (ORR), duration of response (DOR), and disease control rate (DCR) were set as key secondary endpoints.

The median PFS in the Datroway group was 6.9 months. This was an improvement over the 4.9 months in the chemotherapy group, reducing the risk of disease progression or death by 37%.

The ORR was 36.4% in the Datroway group and 22.9% in the chemotherapy group, while the median DOR was 6.7 months and 5.7 months, respectively.

Median OS was 18.6 months in the Datroway group and 18.3 months in the chemotherapy group, with no statistically significant difference at the time of analysis.

In terms of safety, the most commonly reported adverse events were stomatitis, nausea, fatigue, alopecia, constipation, vomiting, and dry eye.

Serious adverse events occurred in 3.1% of patients treated with Datroway. Major serious AEs included interstitial lung disease (ILD, 1.1%), vomiting (0.6%), diarrhea (0.6%), and anemia (0.6%). Fatal outcomes occurred in 0.3% of patients, with ILD cited as the cause.

Potential as a first-Line treatment for triple-negative breast cancer (TNBC)

TROP2-targeted ADCs are creating a new competitive landscape in breast cancer treatment. Currently, the first drug of this mechanism to be commercialized is Gilead's 'Trodelvy' (sacituzumab govitecan). Trodelvy has been approved for the treatment of TNBC in the U.S., Europe, and South Korea.

Datroway has entered the market, pursuing indication expansions focused on breast cancer and non-small cell lung cancer.

Both treatments show promise as first-line treatments for TNBC.

In previously untreated metastatic TNBC, primary treatment options have been limited, except for the immune checkpoint inhibitor 'Keytruda' (pembrolizumab). Analysis suggests that, for PD-L1-negative patients who lack other options besides chemotherapy, the role of TROP2-targeted ADCs is likely to expand.

In the Phase 3 TROPION-Breast02 study, Datroway significantly improved both PFS and OS compared with conventional chemotherapy in the first-line treatment of metastatic TNBC, where immunotherapy is difficult.

The study results showed a PFS of 10.8 months for the Datroway group and 5.6 months for the chemotherapy group, nearly a twofold difference. OS was 23.7 months and 18.7 months, respectively, and both metrics were statistically significant.

ADC anticancer drug 'Trodelvy'

Trodelvy also demonstrated efficacy. The Phase 3 study, named ASCENT-03, compared Trodelvy with chemotherapy.

In the study, Trodelvy had a median PFS of 9.7 months, compared with 6.9 months for chemotherapy. It was also shown to reduce the risk of disease progression or death by 38%.

While OS was not yet mature at the time of the primary analysis, a trend of a continuously widening gap in PFS2 between the treatment and control groups has been confirmed, raising the possibility of future OS improvement.

Gilead is also conducting the ASCENT-04 study to evaluate the efficacy of the Trodelvy + Keytruda combination. This combination has reportedly achieved PFS improvement compared to chemotherapy + Keytruda. Expects suggests that Trodelvy + Keytruda is highly likely to become the new standard of care for first-line TNBC treatment, regardless of PD-L1 expression levels.