Analysis of drug-related interstitial lung disease (ILD) inpatients (pts) treated with datopotamab deruxtecan (Dato-DXd).

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Background: ILD is a potentially serious adverse event seen with many cancer therapies, including checkpoint inhibitors. Factors like smoking and disease pathophysiology have been suspected to potentially increase ILD risk. Dato-DXd, a TROP2-directed antibody drug conjugate, is being evaluated in multiple tumor types. We describe ILD incidence and severity across 5 studies of Dato-DXd in pts with advanced solid tumors. Methods: Pts with non-small cell lung cancer (NSCLC) or breast cancer (BC) who received 6 mg/kg Dato-DXd monotherapy in the TROPION-Lung01, -Lung05, -Breast01 and -PanTumor01 studies were pooled. Additional pts with other solid tumor types (prostate, esophageal, gastroesophageal, pancreatic, small cell lung, urothelial, ovarian, endometrial, colorectal, and biliary tract cancers) receiving Dato-DXd monotherapy in TROPION-PanTumor01 and -PanTumor03 were analyzed separately. An independent adjudication committee retrospectively reviewed potential ILD/pneumonitis cases using imaging and clinical data to assess if the event was drug-related ILD. Adjudicated drug-related ILD events are reported. Results: 927 pts with NSCLC (484) or BC (443) were included in the pooled analysis. Median (range) duration of treatment was 5.5 (0.7, 29.9) months. Overall adjudicated drug-related ILD incidence was 5% (43 pts; 28 grade [Gr] 1-2, 15 Gr 3-5); this was largely driven by the NSCLC pt subgroup (Table). Median (range) time to first onset and duration of first event were 44.0 (7.0, 237) and 39.0 (4.0, 96)days, respectively. ILD associated with dose reduction, drug interruption, or drug withdrawal occurred in 3 (<1%), 13 (1%), and 24 (3%) pts, respectively. In pts with NSCLC, 8 fatal events were observed (7 in TROPION-Lung01, 1 in TROPION-Lung05), 5 of which were attributed to disease progression by investigator. An additional 9 cases of ILD have been reported in 272 pts (3%; Gr 3-5, 2%) across multiple tumor indications enrolled in TROPION-PanTumor01 and -PanTumor03 (Table). Conclusions: Cases ofadjudicateddrug-related ILD seen with Dato-DXd monotherapy were mainly low grade. Gr ≥3 events have been reported, highlighting the need for careful monitoring and adherence to management guidelines. ILD incidence was numerically higher in NSCLC; risk factors for Dato-DXd-related ILD are under investigation. Clinical trial information: NCT05104866; NCT05374512; NCT05489211; NCT04656652; NCT03401385.