Two Phase 3 Trials of Datopotamab Deruxtecan Plus DurvalumabInitiated in Patients Across Two Breast Cancer Subtypes

The first patient has been dosed in two global, randomized phase 3 trials evaluating the efficacy and safety of Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) datopotamab deruxtecan (Dato-DXd) in combination with durvalumab, AstraZeneca’s anti-PD-L1 therapy, in two types of breast cancer. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca. TROPION-Breast04 is evaluating neoadjuvant datopotamab deruxtecan plus durvalumab followed by adjuvant durvalumab with or without chemotherapy in patients with stage II-III triple negative breast cancer (TNBC) or hormone receptor (HR) low, HER2 low or negative breast cancer. TROPION-Breast05 is evaluating datopotamab deruxtecan alone and in combination with durvalumab in patients with locally recurrent inoperable or metastatic TNBC whose tumors express PD-L1 (CPS ≥ 10). Approximately 300,000 people worldwide are diagnosed annually with TNBC, accounting for approximately 15% of all breast cancer diagnoses. 1,2 TNBC is characterized by its aggressive nature and high likelihood of recurrence and progression regardless of stage.3 Standard treatment for patients with early-stage disease (stage II-III) is typically chemotherapy alone or in combination with immunotherapy prior to tumor resection. 6 For patients with metastatic disease, standard first-line treatment can include chemotherapy alone or in combination with immunotherapy.2,3,4 In addition to patients with TNBC, TROPION-Breast04 will enroll patients with HR low, HER2 low or negative breast cancer whose tumors express low levels of hormone receptors(estrogen and/or progesterone receptor levels 1% to < 10%). Patients with HR low, HER2 low or negative disease have historically been excluded from TNBC research astheir tumors are not triple negative. However, these patients tend to have

worse outcomes relative to those with hormone receptor-strongly positive tumors (estrogen and/or
progesterone receptor levels ≥ 10%) on standard endocrine therapies. 5
“While the addition of immune checkpoint inhibitors to chemotherapy has led to survival improvements for
patients with triple negative breast cancer, the overall prognosis for these patients remains poor,” said Mark
Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “These two phase 3 trials
will evaluate whether combining datopotamab deruxtecan, a TROP2 directed antibody drug conjugate, with
durvalumab may offer a more effective option for patients across different settings of breast cancer.”
“In an early phase trial, the datopotamab deruxtecan and durvalumab combination has shown robust and
durable tumor responses and a manageable safety profile in patients with previously untreated advanced
triple negative breast cancer,” said Cristian Massacesi, Chief Medical Officer and Oncology Chief
Development Officer, AstraZeneca. “The initiation of the TROPION-Breast04 and TROPION-Breast05
phase 3 trials underscores our confidence in this promising combination and our commitment to researching
its potential across multiple settings of triple negative breast cancer and in HR low disease.”
Daiichi Sankyo and AstraZeneca have two additional ongoing phase 3 trials evaluating datopotamab
deruxtecan in TNBC. TROPION-Breast02 is evaluating datopotamab deruxtecan versus chemotherapy in
patients with previously untreated locally recurrent inoperable or metastatic TNBC who are not candidates
for anti-PD-1/PD-L1 therapy. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without
durvalumab versus investigator’s choice of therapy in patients with stage I to III TNBC with residual
disease after neoadjuvant therapy.

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