1205MO Updated analysis of DESTINY-Gastric02: A phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable/metastatic gastric/gastroesophageal junction (GEJ) cancer who progressed on or after trastuzumab-containing regimen

Primary results of DESTINY-Gastric02 (NCT04014075; data cutoff [DCO] April 9, 2021), a single-arm, phase II trial of T-DXd in Western pts with HER2+ gastric/GEJ cancer, demonstrated a confirmed objective response rate (cORR) of 38.0% (95% CI, 27.3-49.6), and safety consistent with the established T-DXd safety profile. We report OS and updated efficacy and safety. Pts with centrally confirmed HER2+ (IHC3+ or IHC2+/ISH+ biopsy after progression on trastuzumab-based therapy) unresectable/metastatic gastric/GEJ cancer who progressed on or after 1L therapy received T-DXd 6.4 mg/kg Q3W. The primary endpoint was cORR per RECIST v1.1 by independent central review (ICR). Progression-free survival (PFS) by ICR, duration of response (DOR) by ICR, OS, and patient-reported outcomes based on the European Organization for Research and Treatment of Cancer 5-dimension 5-levels (EQ-5D-5L) quality-of-life (QoL) and Functional Assessment of Cancer Therapy-Gastric (FACT-GA) questionnaires were secondary endpoints. At DCO (November 8, 2021), 79 pts from the US/EU had received T-DXd. 76 pts (96.2%) had received 1 prior line of therapy and 3 (3.8%) had received 2 lines. With a median duration of follow up of 10.2 mo, 10 pts (12.7%) remained on treatment. Median OS was 12.1 mo (95% CI, 9.4-15.4); landmark 12-mo OS rate was 50.6%. cORR was 41.8% (33/79; 4 complete and 29 partial responses). Median DOR was 8.1 mo (95% CI, 5.9-NE). Median PFS was 5.6 mo (95% CI, 4.2-8.3). All pts experienced ≥1 treatment-emergent adverse event (TEAE); 55.7% experienced grade ≥3 TEAEs. The most common TEAEs were nausea (67.1%), vomiting (44.3%) and fatigue (57.0%). Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 pts (10.1%); 6 (7.6%) had grade 1-2 and 2 (2.5%) had grade 5. At DCO (April 9, 2021), QoL assessed by EQ-5D-5L and FACT-GA had been maintained over the treatment course. T-DXd continues to demonstrate substantial clinical benefit and a tolerable safety profile in 2L+ Western pts with HER2+ unresectable/metastatic gastric/GEJ cancer.