Daiichi Sankyo and AstraZeneca Announce Updated Phase 1 Data of TROP2 ADC Datopotamab Deruxtecan in Triple-Negative Breast Cancer

On December 7, Daiichi Sankyo and AstraZeneca announced the latest data from the Phase 1 trial TROPION-PanTumor01 study of the TROP2-targeted antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd, DS-1062a) in treating triple-negative breast cancer (TNBC). This data was disclosed in an oral presentation (GS1-05) at the 2021 San Antonio Breast Cancer Symposium (#SABCS21).

TNBC Accounts for Approximately 10% to 15% of Breast Cancer Cases

TROPION-PanTumor01 is an open-label, multicenter, first-in-human Phase 1 clinical trial evaluating the safety, tolerability, and preliminary efficacy of Dato-DXd in advanced or metastatic solid tumors. Patients enrolled include those with NSCLC, TNBC, HR-positive/HER2-negative breast cancer, small cell lung cancer, urothelial cancer, gastric and gastroesophageal junction adenocarcinoma. These patients had previously received a median of 3 prior lines of therapy (range: 1-10), including taxanes (91%), platinum-based chemotherapy (52%), immunotherapy (43%), and ADCs based on topoisomerase I inhibitors.

According to the blinded independent central review assessment, after a median follow-up of 7.6 months (range: 4-13 months), the objective response rate (ORR) was 34% (15/44) among 44 patients treated with datopotamab deruxtecan (6mg/kg [n=42] and 8mg/kg [n=2]), including 14 cases of complete/partial response (CR/PR) and 1 case of CR/PR pending confirmation, with an additional 17 patients having stable disease (SD). As of July 30, 2021, the median duration of response (DOR) was not reached (range: 2.7–over 7.4 months), and the disease control rate (DCR) was 77%.

Source: Daiichi Sankyo Official Website

Subgroup analysis showed that in 27 patients with measurable lesions who had not previously received ADC treatment, the median follow-up was 8.8 months (range: 4-13 months). The ORR in the Dato-DXd treatment group was 52% (14/27), including 13 cases of CR/PR, 1 case of unconfirmed CR/PR, and 9 cases of SD, with a DCR of 81%.

In terms of safety, the overall safety profile of Dato-DXd in TROPION-PanTumor01 was consistent with previous reports, with no new safety signals identified. Treatment-emergent adverse events (TEAEs) occurring in ≥15% of patients included nausea, stomatitis, vomiting, fatigue, alopecia, mucosal inflammation, constipation, headache, decreased lymphocyte count, decreased neutrophil count, pyrexia, anemia, pruritus, hypokalemia, diarrhea, and cough. Grade 3 or higher treatment-related TEAEs occurred in 23% of patients. No cases of interstitial lung disease (ILD) were observed.

AstraZeneca’s Chief Medical Officer and Chief Development Officer for Oncology, Dr. Cristian Massacesi, stated that based on the data from the triple-negative breast cancer cohort of Dato-DXd in the TROPION-PanTumor01 trial, the two companies are planning to initiate a registrational Phase 3 clinical study.

Currently, according to the Insight database, Dato-DXd already has two Phase III clinical trials ongoing, targeting NSCLC and HR-positive/HER2-negative breast cancer. Triple-negative breast cancer is expected to be the next cancer type to enter Phase III registrational clinical trials.

Source: Insight Database (http://db.dxy.cn/v5/home/)

Note: The original text has been abridged.