Datopotamab Deruxtecan Improved Progression-Free Survival vs. Chemotherapy in Patients with Previously Treated Non-Small Cell Lung Cancer in TROPION-Lung01 Phase III Trial

TROPION-Lung05 results
Initial results from the TROPION-Lung05 Phase II trial showed datopotamab deruxtecan demonstrated encouraging antitumour activity in patients with heavily pretreated locally advanced or metastatic NSCLC with actionable genomic alterations including those with EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements. These data were presented at the ESMO 2023 Congress on Saturday, 21 October (1314MO).

In the overall population (n=137), datopotamab deruxtecan demonstrated a confirmed ORR of 35.8%, including four CRs and 45 partial responses, and a disease control rate (DCR) of 78.8%. Median PFS was 5.4 months. In patients with EGFR mutations (n=78), the largest subgroup, datopotamab deruxtecan demonstrated an ORR of 43.6% and DCR of 82.1%.

The most common Grade 3 or higher TRAEs were stomatitis (10%), anaemia (6%), decreased appetite (4%) and fatigue (4%). There were five ILD events (4%) adjudicated as drug-related by an independent committee, including four Grade 1 or 2 events and one Grade 5 event.

Non-small cell lung cancer
More than one million people worldwide are diagnosed with advanced NSCLC each year.^2,3 Approximately 30% and 70% of NSCLC tumours are of squamous or non-squamous histology, respectively, the latter including adenocarcinoma and large cell carcinoma.¹ While immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive chemotherapy.^4-6 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC in the absence of other treatment options and despite limited effectiveness and known side effects.^4-6

TROP2, a transmembrane glycoprotein, is broadly expressed in a large majority of NSCLC tumours.⁷ There are currently no TROP2-directed ADCs approved for the treatment of lung cancer.^8,9

TROPION-Lung01
TROPION-Lung01 is an ongoing global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) versus docetaxel (75 mg/m²) in patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations previously treated with at least one therapy. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, time to response, DCR as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients at sites in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

TROPION-Lung05
TROPION-Lung05 is an ongoing global, multicenter, single-arm, open-label Phase II study evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in patients with locally advanced or metastatic NSCLC with actionable genomic alterations with disease progression on or after at least one tyrosine kinase inhibitor and at least one regimen of platinum-based chemotherapy (with or without other systemic therapies). Patients with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET, or MET and who received up to four prior lines of treatment were eligible for the study.

The primary trial endpoint is ORR as assessed by BICR. Secondary efficacy endpoints include DOR, best percentage change in the sum of diameters of measurable tumours, DCR, clinical benefit rate, PFS, time to response and OS. Safety endpoints include treatment emergent adverse events and other safety parameters. TROPION-Lung05 enrolled 137 patients globally. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of six ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive development programme called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumours, including NSCLC, triple-negative breast cancer and HR positive, HER2 low or negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.