Results will be presented on 6 June in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (#9004).
More than one million people are diagnosed with advanced stage NSCLC each year.1,2 While 1st-line treatment with immune checkpoint inhibitors with or without chemotherapy has improved outcomes for patients with NSCLC without AGAs, like EGFR or ALK, most patients eventually experience disease progression.3-5 TROP2 is a protein expressed in more than 90% of NSCLC tumours; there are currently no TROP2-directed ADCs approved for the treatment of lung cancer.6-8 Across previously untreated and pretreated patients, an objective response rate (ORR) of 38% was observed (95% confidence interval [CI], 26-51) in patients receiving doublet datopotamab deruxtecan plus pembrolizumab (Merck & Co., Inc., Rahway, NJ, USA), an anti-PD-1 therapy. In patients receiving triplet datopotamab deruxtecan plus pembrolizumab and platinum chemotherapy, an ORR of 49% was observed (95% CI, 37-61). Disease control rates (DCR) of 84% and 87% were observed in the doublet and triplet cohorts, respectively. Median duration of response (DoR) was not reached across cohorts. Although immature, median progression-free survival (PFS) was 8.3 months (95% CI, 6.8-11.8) in the doublet cohort and 7.8 months (95% CI, 5.6-11.1) in the triplet cohort. Response rates were highest in previously untreated patients with ORRs of 50% (95% CI, 32-68) and 57% (95% CI, 42-70) observed in the doublet and triplet cohorts, respectively, with a consistent DCR of 91% observed across cohorts. Yasushi Goto, MD, Division of Internal Medicine and Thoracic Oncology, National Cancer Center HospitalCancer Center Hospital, Tokyo, Japan, and investigator in the trial, said: “Nearly all patients with advanced non-small cell lung cancer experience disease progression following initial therapy, underscoring the need for novel therapeutic approaches across treatment lines. The updated results from TROPION-Lung02 signal the potential for datopotamab deruxtecan combinations to improve outcomes for patients with non-small cell lung cancer and are a promising development in the pursuit of a new standard treatment option beyond immunotherapy.” Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “With more patients and nearly a year of additional follow-up, the updated TROPION-Lung02 results show that datopotamab deruxtecan continues to elicit promising and durable responses in a diverse subset of patients with non-small cell lung cancer. These early data give us confidence in the ongoing Phase III development programme evaluating datopotamab deruxtecan combinations as potential first-line treatment options for patients with advanced lung cancer across tumour histologies and PD-L1 expression levels.” The safety profiles of datopotamab deruxtecan-based combinations were consistent with previous data with no new safety signals observed. Grade 3 or greater treatment-related adverse events (TRAEs) occurred in 31% of patients receiving doublet therapy and 58% of patients receiving triplet therapy. The most frequent adverse events of any Grade in the doublet and triplet cohorts, respectively, were stomatitis (56% and 35%), nausea (41% and 47%), anaemia (21% and 48%) and fatigue (31% and 37%). Across treatment cohorts, there were 27 interstitial lung disease (ILD) or pneumonitis events adjudicated as drug-related by an independent committee. The percentage of ILD events was similar across cohorts. The majority of ILD events were low grade with 23 Grade 1 or Grade 2 and four Grade 3 events. No Grade 4 or Grade 5 ILD events or Grade 5 TRAEs were observed. In the doublet cohort of TROPION-Lung02, 58% of patients were previously untreated and 42% were previously treated with platinum chemotherapy (38%) or immunotherapy (19%). In the triplet cohort, 75% of patients were previously untreated and 25% were previously treated with platinum chemotherapy (24%) or immunotherapy (25%). Eighty percent of patients in the doublet cohort and 73% of patients in the triplet cohort had PD-L1 tumour proportion scores of less than 50%, including 36% and 40% of patients who had PD-L1 tumour proportion scores of less than 1% in the doublet and triplet cohorts, respectively. As of the April 7, 2023 data cut-off, 36% and 46% of patients remained on the doublet and triplet therapy, respectively. ORR, %i (confirmed and pending) (95% CI)
CR, % (pending confirmation)
PR, % (pending confirmation)
Median DoR (months) (95% CI)
Median PFS (months) (95% CI)
ORR, %i (confirmed and pending) (95% CI)
CR, % (pending confirmation)
PR, % (pending confirmation)
Median DoR (months) (95% CI)
CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; NR, not reached; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease iORR is CR + PR iiDCR is best overall response of confirmed CR + confirmed PR + SD
Most patients with NSCLC have tumours that do not express a known AGA (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET).9-11 The current 1st-line standard of care for these patients is treatment with immune checkpoint inhibitors with or without platinum-based chemotherapy. Approximately 40-60% of tumours will not respond to this initial treatment and while these therapies may improve survival for patients whose tumours do respond, most will experience disease progression.5,7 The primary endpoints of TROPION-Lung02 are dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include ORR, DoR, PFS as assessed by investigator, overall survival, pharmacokinetics and anti-drug antibodies for datopotamab deruxtecan and pembrolizumab. 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. 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 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. By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death. 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 Twitter @AstraZeneca. 1. Siegel R, et al. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7-33. 2. World Health Organisation. International Agency for Research on Cancer. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed June 2023. 5. Paz-Ares L, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020;15(10):1657-1669. 6. Mito R, et al. Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol Int. 2020;70(5):287-294. 8. American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html. Accessed June 2023. 11. Adib E, et al. Variation in Targetable Genomic Alterations in Non-Small Cell Lung Cancer by Genetic Ancestry, Sex, Smoking History, And Histology. Genome Med. 2022; 14(1): 39.