Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing head and neck tumors: Outcomes from DESTINY-PanTumor02 (DP-02).

person Funda Meric-Bernstam Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Funda Meric-Bernstam, Seung Tae Kim, Napa Parinyanitikul, Alberto Moreno, Chia-Chi Lin, Dmitry Gornastolev, Jarin Chindaprasirt, Iwona A. Lugowska, Daniil Stroyakovskiy, Jacek Jassem, Michelle L. Harrison, Vikas S. Ostwal, Flavia Michelini, Lindsey Jung, Nataliya Kuptsova-Clarkson, Soham D. Puvvada, Hui Kong Gan

Authors person Funda Meric-Bernstam Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Funda Meric-Bernstam, Seung Tae Kim, Napa Parinyanitikul, Alberto Moreno, Chia-Chi Lin, Dmitry Gornastolev, Jarin Chindaprasirt, Iwona A. Lugowska, Daniil Stroyakovskiy, Jacek Jassem, Michelle L. Harrison, Vikas S. Ostwal, Flavia Michelini, Lindsey Jung, Nataliya Kuptsova-Clarkson, Soham D. Puvvada, Hui Kong Gan Organizations Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, Samsung Medical Center, Seoul, South Korea, King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand, University Reina Sofia Hospital and IMIBIC, Córdoba, Spain, National Taiwan University Hospital, Taipei, Taiwan, Hadassah Medical Moscow – Oncology Department, Moscow, Russian Federation, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland, Moscow City Oncology Hospital No. 62, Moscow, Russian Federation, Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland, Chris O’Brien Lifehouse, Sydney, NSW, Australia, Tata Memorial Hospital, Mumbai, India, Translational Medicine, Oncology R&D, AstraZeneca, Waltham, MA, AstraZeneca, Gaithersburg, MD, Oncology R&D, AstraZeneca, Gaithersburg, MD, Austin Health, Heidelberg, VIC, Australia Abstract Disclosures Research Funding This study is sponsored by AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). Background: In DP-02, T-DXd demonstrated an objective response rate (ORR) by investigator (INV) of 37.1% (95% CI 31.3, 43.2) and clinically meaningful survival outcomes in 267 pretreated pts with HER2-expressing tumors. In this post-hoc analysis, we report outcomes and characterize those with an objective response (OR) in a subset of pts with head and neck cancers (previously included in the ‘other tumor’ cohort), most of which were salivary gland tumors. Methods: This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in pts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced/metastatic disease after ≥1 systemic treatment or without treatment options. The primary endpoint was confirmed ORR by INV. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), and safety. Exploratory endpoints included efficacy outcomes by HER2 expression. Results: At data cutoff (June 2023), 24 pts with head and neck tumors (n=19 salivary gland, n=3 squamous cell carcinoma [SCC], n=1 adenoid cystic carcinoma, n=1 lacrimal gland) had received treatment (median [m] follow up: 20.8 months [range: 4.7–31.6]). Of these pts, 15 (62.5%) had received ≥2 prior treatment regimens. 10/24 pts (41.7%; 95% CI 22.1, 63.4; n=8 salivary gland, n=1 SCC, n=1 lacrimal gland) had a confirmed OR by INV; 9 responders had received prior radiation therapy, and 4 had known PD-L1 immune cell status ≥1%. The Table shows efficacy outcomes in all pts and by HER2 expression (central testing). Grade (G) ≥3 drug-related adverse events occurred in 10/24 (41.7%) pts. Adjudicated drug-related interstitial lung disease / pneumonitis occurred in 3/24 (12.5%) pts (n=1 G1; n=1 G2; n=1 G5). Conclusions: T-DXd showed clinically meaningful benefit in pretreated pts with head and neck tumors. Responses were observed across HER2 expression levels. Safety was consistent with the known profile. These data support T-DXd as a potential treatment for pretreated pts with HER2-expressing head and neck tumors. Clinical trial information: NCT04482309. All pts HER2 IHC 3+ HER2 IHC 2+ HER2 IHC 0 HER2 unknown n 24 7 6 4 7 Pts with OR, n 10 4 1 1 4 ORR, % (95% CI) 41.7 (22.1, 63.4) 57.1 (18.4, 90.1) 16.7 (0.4, 64.1) 25.0 (0.6, 80.6) 57.1 (18.4, 90.1) mDOR, months (95% CI)* 22.1 (2.8, NE) 22.1 (4.1, NE) 2.8 NR NR (10.9, NE) mPFS, months (95% CI) 12.4 (8.7, 23.4) 23.4 (9.7, NE) 7.1 (2.9, NE) 6.5 (4.2, NE) 12.5 (8.8, NE) DCR at 12 weeks, % (95% CI) 87.5 (67.6, 97.3) 100 (59.0, 100) 66.7 (22.3, 95.7) 75.0 (19.4, 99.4) 100 (59.0, 100) By INV. Local HER2 status confirmed by central testing; upon reanalysis, some pts were IHC 0/unknown. *Responders only; CIs omitted where n=1. NE, not evaluable; NR, not reached.

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