MA03.02 TROPION-PanTumor01: Updated Results From the NSCLC Cohort of the Phase 1 Study of Datopotamab Deruxtecan in Solid Tumors

Abstract

Datopotamab deruxtecan (Dato-DXd) is an antibody drug conjugate (ADC) composed of a TROP2-directed monoclonal antibody conjugated to a topoisomerase I inhibitor via a tetrapeptide-based cleavable linker. Dato-DXd demonstrated encouraging antitumor activity in patients with advanced/metastatic non-small cell lung cancer (NSCLC) in preliminary analyses from TROPION-PanTumor01. Based on this study, Dato-DXd 6 mg/kg has been selected as the recommended dose for the phase 3 TROPION-Lung01 trial. Here we report updated results in NSCLC. TROPION-PanTumor01 (NCT03401385) is a phase 1 dose-escalation/expansion study evaluating Dato-DXd in patients with solid tumors. Patients were unselected for TROP2 expression and had measurable disease per RECIST version 1.1; patients with stable/treated brain metastases were permitted. The primary objective was safety and tolerability. Secondary objectives were efficacy and pharmacokinetics. The primary analysis in the NSCLC cohort will be performed 6 months after enrollment of the last patient, which occurred on 06 October 2020. As of the data cutoff (08 January 2021), enrollment in the NSCLC cohort was complete; 180 patients from the dose-escalation and -expansion phases were treated with Dato-DXd 4 mg/kg (n=50), 6 mg/kg (n=50), or 8 mg/kg (n=80). Overall, 42% of patients were aged ≥65 years and 37% had a history of brain metastases. The median number of prior therapies was 3 (range, 1-9); 83% had prior PD-(L)1 therapy and 96% had prior platinum chemotherapy. Median follow-up was 11.4 months (range, 3.1-25.9 months). Objective response rate by blinded independent central review: 4 mg/kg, 24% (12/50); 6 mg/kg, 26% (13/50); 8 mg/kg, 24% (19/80), including 4 patients (2 each at 4 mg/kg and 6 mg/kg) still ongoing treatment with responses not yet confirmed. Grade ≥3 treatment-emergent adverse events (TEAEs) regardless of causality were reported in 47% of patients across doses. TEAEs seen in ≥30% of patients included (all grade, grade ≥3) nausea (52%, 1%), stomatitis (48%, 2%), alopecia (39%, 0%), and fatigue (32%, 1%). Select TEAEs (all grade, grade ≥3) of decreased neutrophil count/neutropenia (6%, 1%) and diarrhea (16%, 0%) observed with another TROP2-directed ADC were infrequent with Dato-DXd. Drug-related interstitial lung disease, by independent adjudication, occurred in 19 patients (11%): 4 mg/kg (10%, 1 grade 1, 3 grade 2, 1 grade 3); 6 mg/kg (4%, 2 grade 2); 8 mg/kg (15%, 3 grade 1, 5 grade 2, 1 grade 3, 3 grade 5). TEAEs leading to dose reductions/interruptions occurred in 16% and 18% of patients, respectively: 4 mg/kg, 2% and 14%; 6 mg/kg, 8% and 18%; 8 mg/kg, 30% and 21%. Treatment discontinuations due to TEAEs were observed in 15% of patients (4 mg/kg, 14%; 6 mg/kg, 10%; 8 mg/kg, 19%), including some patients with prior dose reductions/interruptions. Primary analysis results from the NSCLC cohort will be presented. Dato-DXd continues to demonstrate promising efficacy and a generally manageable safety profile in heavily pretreated patients with advanced/metastatic NSCLC for whom treatment options are limited.