Datopotamab deruxtecan combinations showed encouraging tumour responses in patients with advanced non-small cell lung cancer

TROPION-Lung02 Phase Ib trial showed datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum-based chemotherapy demonstrated promising clinical activity and no new safety signals in both previously untreated or pretreated patients with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs).

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

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 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.”

Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo said: “We continue to be encouraged by the findings from TROPION-Lung02, the first trial to evaluate the combination of a TROP2-directed antibody-drug conjugate and an immune checkpoint inhibitor with or without platinum chemotherapy in patients with advanced non-small cell lung cancer. These data, alongside previous results for datopotamab deruxtecan combined with an immune checkpoint inhibitor, reinforce the potential of these combinations to improve outcomes for patients with different advanced cancers.”

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Related Topics and Keywords

AstraZeneca, datapotamab, datopotamab deruxtecan, non squamous non small cell lung cancer, tumour