DATROWAY® Shows Unprecedented Five-Month Median Overall Survival Benefit vs. Chemotherapy in First-Line Treatment of Metastatic Triple-Negative Breast Cancer (TROPION-Breast02) for Patients Ineligible for Immunotherapy

10/19/2025 – 02:30 AM

• Daiichi Sankyo and AstraZeneca’s DATROWAY also demonstrated a highly statistically significant and clinically meaningful 43% reduction in patients’ risk of disease progression or death

• DATROWAY is the first and only therapy to significantly improve overall survival versus chemotherapy in this patient population

TOKYO & BASKING RIDGE, N.J.–Positive results from the TROPION-Breast02 phase 3 trial, unveiled at the 2025 European Society for Medical Oncology (ESMO) Congress, position DATROWAY^® (datopotamab deruxtecan) as a potential game-changer in the first-line treatment of locally recurrent inoperable or metastatic triple negative breast cancer (TNBC). The study demonstrated statistically significant and clinically meaningful improvements in both overall survival (OS) and progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients for whom immunotherapy was not an option. These findings challenge the current standard of care and offer a new hope for a particularly aggressive form of breast cancer.

DATROWAY, a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN), leverages the targeted delivery of a potent cytotoxic payload to cancer cells expressing the TROP2 protein. This precision approach minimizes off-target effects, potentially leading to improved efficacy and tolerability compared to traditional chemotherapy. The market capitalization of these two companies combined, exceeds a quarter of a trillion USD, meaning the stakes are extremenly high.

The TROPION-Breast02 trial revealed a 5.0-month improvement in median OS with DATROWAY compared to chemotherapy (hazard ratio [HR]=0.79; 95% confidence interval [CI]: 0.64-0.98; p=0.0291). Median OS was 23.7 months for patients treated with DATROWAY versus 18.7 months for those treated with chemotherapy. This OS benefit is particularly noteworthy, as metastatic TNBC has historically proven difficult to treat.

In addition to the OS benefit, DATROWAY reduced the risk of disease progression or death by 43% compared to chemotherapy (HR=0.57; 95% CI: 0.47-0.69; p<0.0001). Median PFS was 10.8 months for patients treated with DATROWAY versus 5.6 months for those treated with chemotherapy. This significant improvement in PFS suggests that DATROWAY can effectively control disease progression and extend the time patients live without their cancer worsening.

Further bolstering the efficacy profile of DATROWAY, the trial demonstrated a more durable treatment response compared to chemotherapy, where confirmed objective response rate (ORR) was 62.5% with DATROWAY, including 29 complete responses (CR) and 173 partial responses (PR) versus 29.3% with chemotherapy, including eight CRs and 86 PRs. Median duration of response (DoR) for patients treated with DATROWAY exceeded one year (12.3 months) versus 7.1 months for those treated with chemotherapy. The higher response rate and longer duration of response underscore the potential of DATROWAY to induce deep and sustained remissions in TNBC patients.

The trial’s design included a diverse patient population, including those with PD-L1 expressing tumors for whom immunotherapy was not an option. At the data cut-off, 14% of patients remained on DATROWAY and 3% on chemotherapy, also suggesting the favorable tolerability profile of DATROWAY.

“In TROPION-Breast02, datopotamab deruxtecan meaningfully extended patients’ lives and nearly doubled their time without disease progression,” said Rebecca Dent, MD, FRCP, Professor and Deputy Chief Executive Officer, National Cancer Centre Singapore, and Principal Investigator for the trial, highlighting the substantial clinical impact of the findings. “These are significant outcomes for patients with metastatic triple negative breast cancer who are not suitable candidates for immunotherapy, and remarkable results considering the trial included a subset of patients with highly aggressive disease who are often excluded from research in this setting.”

While patients receiving DATROWAY were on treatment more than twice as long as those receiving chemotherapy (median duration of treatment of 8.5 versus 4.1 months), they also experienced a lower rate of treatment-related adverse events (TRAEs) associated with discontinuation (4% versus 7%). Grade 3 or higher TRAEs occurred in 33% and 29% of patients in the DATROWAY and chemotherapy arms, respectively. It is important to note that there was one grade 5 interstitial lung disease (ILD) event in the DATROWAY arm adjudicated as drug-related by an independent committee. These safety data reflect the ongoing need for careful monitoring and management of potential adverse events associated with DATROWAY treatment.

“Patients with metastatic triple negative breast cancer have one of the worst prognoses of any breast cancer subtype, and for those who are not candidates for immunotherapy, chemotherapy has long been the first-line standard of care,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, underscoring the urgent need for new treatment options. “The TROPION-Breast02 results show DATROWAY has the potential to replace traditional chemotherapy in this setting and to meaningfully improve survival of patients.”

“The TROPION-Breast02 results show for the first time that these triple negative breast cancer patients may have an alternative to chemotherapy in the first-line setting that can both delay the progression of their disease and prolong their lives,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca, highlighting the transformative potential of DATROWAY. “For DATROWAY to have so significantly improved patient outcomes in the first-line metastatic setting as monotherapy also gives us great confidence in its potential in combination with durvalumab, and in the early-stage, potentially curative setting where our next studies are ongoing.”

Summary of TROPION-Breast02 Results

Daiichi Sankyo and AstraZeneca will also present updated results from the BEGONIA phase 1b/2 trial at ESMO showing DATROWAY in combination with AstraZeneca’s anti-PD-L1 therapy durvalumab continued to demonstrate robust anti-tumor activity as first-line treatment for patients with metastatic TNBC across PD-L1 expression levels and specifically in those with high PD-L1-expressing tumors. These results will be presented on Monday, October 20, 2025.

Daiichi Sankyo and AstraZeneca are evaluating DATROWAY across stages and treatment settings of TNBC in three additional phase 3 trials: TROPION-Breast03, TROPION-Breast04 and TROPION-Breast05.

About TROPION-Breast02
TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of DATROWAY versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumors did not express PD-L1 as well as patients with PD-L1 expressing tumors who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrollment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases.

The dual primary endpoints of TROPION-Breast02 are PFS as assessed by BICR and OS. Key secondary endpoints include PFS as assessed by investigator, ORR, DoR, disease control rate (DCR), pharmacokinetics and safety.

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America .

About Triple Negative Breast Cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year. Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses.

While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three. Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat. For patients with metastatic disease with PD-L1 expressing tumors, the addition of immunotherapy to chemotherapy has improved outcomes in the first-line setting. However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the first-line standard of care.

TROP2 is a protein broadly expressed in several solid tumors, including TNBC. TROP2 is associated with increased tumor progression and poor survival in patients with breast cancer.

About DATROWAY

DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform.

DATROWAY (6 mg/kg) is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.

DATROWAY (6 mg/kg) is approved in Russia and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy, based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the DATROWAY Clinical Development Program

A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other cancer treatments in various settings.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU^® in March 2019 and DATROWAY in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY.

About the ADC Portfolio of Daiichi Sankyo

The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

DATROWAY U.S. Important Safety Information

Indications
DATROWAY^® is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of:

• adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

Contraindications
None.

Warnings and Precautions
Interstitial Lung Disease/Pneumonitis
DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis.

Locally Advanced or Metastatic NSCLC
In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01, ILD/pneumonitis occurred in 7% of patients treated with DATROWAY, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases.

Unresectable or Metastatic Breast Cancer
In the pooled safety population of 443 patients with breast cancer from TROPION-Breast01 and TROPION-PanTumor01, ILD/pneumonitis occurred in 3.6% of patients treated with DATROWAY, including 0.7% of patients with Grade 3. There was one fatal case (0.2%).

Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent).

Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed.

Ocular Adverse Reactions
DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.

In the pooled safety population, ocular adverse reactions occurred in 36% of patients treated with DATROWAY. The most common (≥5%) ocular adverse reactions were dry eye (17%), keratitis (14%), and increased lacrimation (7%).

Advise patients to use preservative-free lubricant eye drops several times daily for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional.

Refer patients to an eye care professional for an ophthalmic exam at treatment initiation, annually while on treatment, at end of treatment, and as clinically indicated.

Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue DATROWAY based on severity.

Stomatitis
DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis.

In the pooled safety population, stomatitis occurred in 63% of patients treated with DATROWAY, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction.

Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY.

Monitor patients for signs and symptoms of stomatitis. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue DATROWAY.

Embryo-Fetal Toxicity
Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman.

Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose.

Adverse Reactions
The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 927 patients. In this pooled safety population, the most common (≥20%) adverse reactions were stomatitis (63%), nausea (52%), fatigue (45%), alopecia (38%), constipation (28%), decreased appetite (23%), rash (23%), vomiting (22%), and musculoskeletal pain (20%).

Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC…

Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer

The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer…

Use in Specific Populations

• Pregnancy: …

• Lactation: …

• Females and Males of Reproductive Potential: Pregnancy Testing: Contraception: Infertility: …

• Pediatric Use: Safety and effectiveness of DATROWAY have not been established in pediatric patients.

• Geriatric Use: …

• Renal Impairment: …

• Hepatic Impairment: …

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including WARNINGS AND PRECAUTIONS, and Medication Guide.

About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world.

Source: Daiichi Sankyo