Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial

• DOI: 10.1200/jco.23.02005
• Publication Date: 2023-10-23T14:49:14Z
• Authors: Funda Meric-Bernstam; Vicky Makker; Ana Oaknin; Do-Youn Oh; Susana Banerjee; Antonio González-...; Kyung Hae Jung; Iwona Ługowska; Luis Manso; Aránzazu Manzano; Bohuslav Melichar; Salvatore Siena; Daniil Stroyakovskiy; Anitra Fielding; Yan Ma; Soham Puvvada; Norah Shire; Jung-Yun Lee
• Keywords: Clinical endpoint

PURPOSE Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)–directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers HER2-mutant non–small-cell lung cancer. Treatments are limited for other solid tumors. METHODS This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced metastatic disease after ≥1 systemic treatment without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary points included safety, duration of response, progression-free survival (PFS), overall (OS). RESULTS At analysis, 267 patients received across seven tumor cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, other. median follow-up 12.75 months. In all patients, the ORR 37.1% (n = 99; [95% CI, 31.3 to 43.2]), with responses cohorts; DOR 11.3 months (95% 9.6 17.8); PFS 6.9 5.6 8.0); OS 13.4 11.9 15.5). HER2 IHC 3+ expression 75), 61.3% 49.4 72.4), 22.1 not reached), 8.2 13.0), 21.1 15.3 29.6). Grade ≥3 drug-related adverse events were observed 40.8% patients; 10.5% experienced adjudicated interstitial (ILD), three deaths. CONCLUSION Our demonstrates durable clinical benefit, meaningful outcomes, safety consistent known profile (including ILD) pretreated tumors receiving T-DXd. Greatest benefit population. These data support potential role as tumor-agnostic therapy