LBA4 Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate (ADC), for triple-negative breast cancer (TNBC): Preliminary results from an ongoing phase I trial

Abstract

Dato-DXd is an ADC comprising a humanized anti-TROP2 IgG1 mAb conjugated to a potent topoisomerase I inhibitor payload (DXd) via a stable tetrapeptide-based cleavable linker. Results from the ongoing phase I TROPION-PanTumor01 (NCT03401385) study showed encouraging antitumor activity of Dato-DXd in heavily pretreated patients (pts) with metastatic (m) NSCLC. Reported here are preliminary results in mTNBC; recruitment is ongoing. TROPION-PanTumor01 is a 2-part study evaluating Dato-DXd IV Q3W in previously treated pts with solid tumors. Based on the dose-escalation phase limited to NSCLC pts, this expansion phase evaluated 6 mg/kg in pts with mTNBC that relapsed/progressed with standard treatment (TX). The primary endpoint was safety/tolerability. Secondary endpoints included efficacy assessed by ORR per RECIST v1.1 by blinded independent central review (BICR). As of the Jan 8, 2021, data cutoff, 24 pts had ≥1 dose (6 mg/kg, n=22; 8 mg/kg, n=2 [treated prior to 6-mg/kg dose selection]), with 18 (75%) still on TX and 6 (25%) discontinued for PD. Median age was 57 y (range, 32-82 y); 71% had ≥3 prior lines of therapy. Prior therapies were taxanes (83%), platinum-based TX (50%), immunotherapy (33%), and sacituzumab govitecan (8%). Among 21 pts (6 mg/kg, n=19; 8 mg/kg, n=2) evaluable for response (≥1 postbaseline tumor assessment or discontinued TX), ORR by BICR was 43% (9 PRs), with 5 confirmed and 4 pending confirmation. The disease control rate was 95% (20/21 pts). Dose reductions due to AEs occurred in 6 pts (25%); no pts discontinued TX due to AEs. Any grade (Gr) and Gr ≥3 TEAEs regardless of causality occurred in 100% and 33% of pts, respectively. Most common TEAEs (any Gr [≥40%], Gr ≥3) were nausea (63%, 0%), stomatitis (63%, 13%), fatigue (42%, 4%), and vomiting (42%, 0%). No Gr ≥3 TEAEs of diarrhea or decreased neutrophil count/neutropenia were reported. No cases of TX-related ILD (adjudicated) were observed. Preliminary results show that Dato-DXd had highly encouraging antitumor activity and a manageable safety profile in pts with refractory mTNBC; further confirmatory studies are warranted.