Datopotamab deruxtecan plus Imfinzi showed 73.6% ORR in 1st-line treatment of metastatic TNBC.- Daiichi Sankyo + AstraZeneca

Among the 53 evaluable patients, there were four CRs and 35 PRs. Responses were observed regardless of PD-L1 expression (low and high tumours) with 82% of patients continuing to respond at the time of data cut-off on 22 July 2022. These data were presented at SABCS on 8 December (abstract #PD11-09).

Twenty-five patients (41.0%) had not received prior treatment for metastatic TNBC. Prior treatments for patients with early-stage disease included radiotherapy (49.2%), anthracyclines (45.9%), taxanes (41.0%), platinum-based chemotherapy (14.8%), hormonal therapy (14.8%) and targeted therapy (4.9%). Seven (11.5%) patients had high PD-L1 expression (tumour area positivity [TAP]?10%) and 53 (86.9%) patients had low PD-L1 expression (TAP<10%). at data cut-off, 45 patients remained on study treatment.></10%).>

The safety profile of datopotamab deruxtecan in combination with Imfinzi was consistent with the known safety profiles of both agents. The most common all-Grade TEAEs occurring in 20% or more of patients were nausea (57.4%), stomatitis (55.7%), alopecia (45.9%), fatigue (39.3%), constipation (39.3%), rash (27.9%) and vomiting (21.3%). Serious TEAEs were observed in 10 patients (16.4%). Treatment discontinuations due to an adverse event occurred in four patients (6.6%). No dose-limiting toxicities were reported. Two cases (3.3%) were adjudicated as treatment-related Grade 1 ILD.

AstraZeneca and Daiichi Sankyo have a broad clinical development programme for datopotamab deruxtecan in TNBC, including the recently initiated global TROPION-Breast03 Phase III trial evaluating datopotamab deruxtecan with and without Imfinzi in patients with Stage I-III TNBC with residual disease after neoadjuvant therapy. The first patients were enrolled in November 2022 and are expected to be dosed in December 2022. SWOG Cancer Research Network Clinical Trials Partnerships (SWOG CTP) is the lead academic group for the trial and a key collaborator in its protocol development, US site selection and planned recruitment and analysis.

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.

: BEGONIA : is an open-label, two-part, multicentre Phase Ib/II trial evaluating Imfinzi in combination with oncology therapies with or without paclitaxel for the 1st-line treatment of metastatic TNBC. Arm 7 of the trial is evaluating the safety, tolerability and preliminary efficacy of datopotamab deruxtecan in combination with Imfinzi in patients with previously untreated, unresectable locally advanced or metastatic TNBC. The primary endpoints are safety and tolerability. The secondary endpoints include investigator-assessed ORR, PFS, DoR and OS.