Datopotamab deruxtecan (Dato-DXd) is an investigational ADC developed by Daiichi Sankyo. It's a TROP2-targeted ADC, part of AstraZeneca's platform, with a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a highly potent topoisomerase inhibitor payload via a plasma-stable, tumor-selective, tetrapeptide-based cleavable linker.

TROPION-Lung05 is a Phase II, single-arm study evaluating Dato-DXd in patients with advanced or metastatic NSCLC with actionable genomic alterations that progressed on or after targeted therapy and platinum-based chemotherapy. 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.

The most common Grade 3 or higher TRAEs were stomatitis, anemia, decreased appetite, and fatigue. There were five  interstitial lung disease events adjudicated as drug-related by an independent committee, including four Grade 1 or 2 events and one Grade 5 event.

Dato-DXd showed encouraging antitumor activity, with a clinically meaningful and durable response, in heavily pretreated patients with NSCLC with actionable genomic alterations. The safety profile was manageable and consistent with prior safety observed with Dato-DXd. 

KOL insights: “TROPION-Lung05; DATO-DXd in patients with actionable mutations post targeted treatment; largely EGFR and ALK; 51% had brain metastases; better responses in EGFR vs ALK; no new toxicity signals.” - Consultant Medical Oncologist, UK

Conclusion: Dato-DXd demonstrated promising antitumor activity in heavily pretreated NSCLC patients with actionable genomic alterations, including EGFR mutations and ALK rearrangements. The treatment maintained a manageable safety profile, characterized by a low incidence of grade ≥3 toxicities, primarily related to hematologic issues or drug-related concerns. Nausea and stomatitis were the predominant adverse events, consistent with prior NSCLC data. Ongoing research, specifically the randomized Phase III TROPION-Lung01 study, continues to evaluate Dato-DXd versus docetaxel in patients with pretreated advanced or metastatic NSCLC, particularly those with actionable genomic alterations.

DelveInsight estimates that the highest market is expected from PDL1 NSCLC segment, followed by EGFR and KRAS by 2032 in the 7MM. NSCLC is increasingly becoming a biomarker-driven market. EGFR is one of the profitable biomarker segment, with blockbuster therapies such as TAGRISSO.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Non-Small Cell Lung Cancer Market Insight and Market Forecast Report

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.