Datopotamab deruxtecan showed an encouraging objective response rate of 32% and a manageable safety profile in patients with metastatic TNBC in TROPION-PanTumor01 Phase I trial.- Daiichi Sankyo + AstraZeneca

Results were presented at the 2022 San Antonio Breast Cancer Symposium (SABCS) (abstract #P6-10-03).

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

Approximately 15% of breast cancers are considered triple-negative and are associated with higher disease recurrence and worse prognosis compared to other breast cancer subtypes. It is estimated that only 12% of patients with metastatic TNBC survive five years after diagnosis and median overall survival is between 12 to 18 months.

In the TNBC cohort of TROPION-PanTumor01 (n=44), datopotamab deruxtecan demonstrated an objective response rate (ORR) of 32%, including one complete response (CR), 13 partial responses (PRs) and 18 cases of stable disease (SD) as assessed by blinded independent central review (BICR). In a subgroup of 27 patients who had not been treated with topoisomerase I inhibitor-based ADCs, the ORR was 44%, including one CR, 11 PRs and 10 cases of SD. The median duration of response (DoR) was 16.8 months across patient groups.

In the overall cohort , datopotamab deruxtecan demonstrated median progression-free survival (PFS) of 4.4 months (95% confidence interval [CI], 3.0-7.3) and median overall survival (OS) of 13.5 months (95% CI, 10.1-16.3). In the subgroup of patients who had not been treated with a topoisomerase I inhibitor, median PFS and OS were 7.3 months (95% CI, 3.0-18.0) and 14.3 months (95% CI, 10.5-NE), respectively. The disease control rate (DCR) was consistent across the overall cohort and previously untreated subgroup at 80% and 81%, respectively.

Patients in the TROPION-PanTumor01 trial were heavily pretreated, receiving a median of three prior regimens in the metastatic setting (range 1-10). Prior treatments included taxanes (93%), anthracyclines (75%), capecitabine (61%), platinum-based chemotherapy (52%), immunotherapy (45%), topoisomerase I inhibitor-based ADCs (32%) and PARP inhibitors (18%). As of data cut-off on 22 July 2022, three patients remained on study treatment.

The safety profile of datopotamab deruxtecan was consistent with previously reported data with no new safety signals identified. The most common Grade 3 or higher treatment-emergent adverse events (TEAEs) were stomatitis (11%), decreased lymphocyte count (7%), fatigue (7%), vomiting (5%), anaemia (2%), decreased neutrophil count (2%) and nausea (2%). Serious TEAEs were reported in nine patients (20.5%). Treatment discontinuation occurred in one patient (2%) due to Grade 1 pneumonitis, which was adjudicated as not treatment-related interstitial lung disease (ILD). No cases of febrile neutropenia or Grade 3 or higher diarrhoea were observed.

Aditya Bardia, Director, Breast Cancer Research Program, Mass General Cancer Center and Associate Professor of Medicine, Harvard Medical School, and investigator in the TROPION-PanTumor01 trial, said: “Triple-negative breast cancer is the most aggressive subtype of breast cancer with the average survival rate of less than 18 months for patients with pretreated metastatic disease. The durable tumour response and disease control seen with datopotamab deruxtecan in patients with pretreated triple-negative breast cancer are encouraging, particularly in those patients who had not received previous treatment with topoisomerase I inhibitor-based antibody drug conjugate.”

TROPION-PanTumor01 : TROPION PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with non-small cell lung cancer (NSCLC) to assess the safety and efficacy of datopotamab deruxtecan to determine the recommended dose for expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, TNBC, HR-positive, HER2-low or negative breast cancer, small cell lung cancer (SCLC), urothelial, gastric, pancreatic, castration-resistant prostrate and oesophageal cancer. Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, time to response, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.