Abstract 1869TiP
Background
Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in both breast and gastric cancer. However, HER2-targeting therapies are not approved beyond these malignancies despite a high prevalence of HER2 expression across cancers of epithelial origin. T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor payload. In a cohort of pretreated patients with multiple HER2-expressing tumors, T-DXd demonstrated promising antitumor activity, with an investigator-assessed confirmed objective response rate of 40.9% (9 of 22 patients) and median progression-free survival of 11.1 months (95% CI, 5.4-20.5 months; Tsurutani J, et al. Cancer Discov. 2020;10:688-701). Here we describe the phase 2 DESTINY-PanTumor02 trial evaluating T-DXd in patients with select HER2-expressing solid tumors.
Trial design
DESTINY-PanTumor02 is an open-label, multicenter, multicohort, phase 2 study evaluating T-DXd for the treatment of patients with select HER2-expressing locally advanced, unresectable, or metastatic tumors. The study will consist of 7 cohorts of patients (n≈40 each) with urothelial bladder, biliary tract, cervical, endometrial, ovarian, pancreatic, or rare tumors (tumors excluding those in the other cohorts and breast, gastric, colorectal, and non-small cell lung cancer). Patients are required to have disease progression following ≥1 prior systemic treatment for advanced or metastatic disease or have no satisfactory alternative treatment options. Prior HER2-targeting therapy is allowed. The primary endpoint is investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include duration of response, disease control rate, progression-free survival (all per investigator assessment according to RECIST 1.1), overall survival, safety, pharmacokinetics, and immunogenicity.
Clinical trial identification
NCT04482309.
Editorial acknowledgement
Medical editorial assistance was provided by ArticulateScience LLC. and funded by AstraZeneca Pharmaceuticals LP.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
F. Meric-Bernstam: Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Inflection Biosciences; Financial Interests, Personal, Advisory Role: Samsung Bioepis; Financial Interests, Personal, Advisory Role: Spectrum Pharmaceuticals; Financial Interests, Personal, Advisory Role: Aduro Biotech; Financial Interests, Personal, Advisory Role: Origimed; Financial Interests, Personal, Advisory Role: Xencor; Financial Interests, Personal, Advisory Role: Debiopharm Group; Financial Interests, Personal, Advisory Role: Mersana; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Silverback Therapeutics; Financial Interests, Personal, Advisory Role: Immunomedics; Financial Interests, Personal, Advisory Role: IBM Watson Health; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: PACT Pharma; Financial Interests, Personal, Advisory Role: eFFECTOR Therapeutics; Financial Interests, Personal, Advisory Role: Jackson Laboratory for Genomic Medicine; Financial Interests, Personal, Advisory Role: Kolon Life Sciences; Financial Interests, Personal, Advisory Role: PAREXEL; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Tyra Biosciences; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Zentalis; Financial Interests, Personal, Advisory Role: Alkermes; Financial Interests, Personal, Advisory Role: Infinity Pharmaceuticals; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Other, Travel, accommodations, expenses: Taiho Pharmaceutical; Financial Interests, Personal, Other, Travel, accommodations, expenses: Beth Israel Deaconess Medical Center; Financial Interests, Personal, Other, Honoraria: Mayo Clinic; Financial Interests, Personal, Other, Honoraria: Rutgers Cancer Institute of New Jersey; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Debiopharm Group; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Aileron Therapeutics; Financial Interests, Institutional, Research Grant: PUMA Biotechnology; Financial Interests, Institutional, Research Grant: CytomX Therapeutics; Financial Interests, Institutional, Research Grant: Jounce Therapeutics; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: eFFECTOR Therapeutics; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Seattle Genetics. C. Anoka: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. A. Dobrowolska: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. A. Chaudhry: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Rowbottom: Financial Interests, Personal, Full or part-time Employment, The employment detailed above for AstraZeneca and GlaxoSmithKline is/was contract work: AstraZeneca; Financial Interests, Personal, Full or part-time Employment, The employment detailed above for AstraZeneca and GlaxoSmithKline is/was contract work. : GlaxoSmithKline; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Gustavson: Financial Interests, Personal, Full or part-time Employment, Self and immediate family member : AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Puvvada: Financial Interests, Personal, Full or part-time Employment: AstraZeneca.