A pooled analysis of the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 trials demonstrated that datopotamab deruxtecan (Dato-DXd) achieved significant clinical responses in patients with previously treated advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). These findings, including progression-free survival (PFS) and overall survival (OS) results, were presented during a late-breaking proffered paper session at the 2024 ESMO Asia Congress.
Datopotamab deruxtecan is a TROP2-targeting antibody-drug conjugate (ADC) developed by Daiichi Sankyo and AstraZeneca. In the pooled analysis of 117 patients from both trials (TROPION-Lung05, n=78; TROPION-Lung01, n=39), the confirmed objective response rate (ORR) was 42.7% (95% CI: 33.6-52.2). Five complete responses (CR), 45 partial responses (PR), and 48 stable disease (SD) cases were reported. The median duration of response (DOR) was 7.0 months, with a disease control rate (DCR) of 86.3%. Median PFS was 5.8 months and median OS was 15.6 months.
“Myung-Ju Ahn, MD, PhD, of Samsung Medical Center, stated that while EGFR tyrosine kinase inhibitors (TKIs) have improved outcomes for EGFR-mutated NSCLC patients, most eventually experience disease progression. These results suggest datopotamab deruxtecan could provide a new option for these patients,” Ahn said.
Among patients previously treated with osimertinib, 96 individuals showed a confirmed ORR of 44.8% (95% CI: 34.6-55.3). Similar outcomes were observed in this subgroup with a median DOR of 6.9 months, DCR of 85.4%, median PFS of 5.7 months, and median OS of 14.7 months.
The safety profile of datopotamab deruxtecan was consistent with previous reports, with no new safety concerns identified. Common treatment-related adverse events (TRAEs) included stomatitis (59%), alopecia (49%), nausea (46%), and fatigue (18%). Grade 3 or higher TRAEs were seen in 23% of patients, with no grade 4 or 5 events for stomatitis, ocular surface issues, or drug-related interstitial lung disease (ILD).
Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, commented that the data from TROPION-Lung05 and TROPION-Lung01 trials support the regulatory submission of datopotamab deruxtecan in the U.S. and its potential as a new treatment option for this patient group.
Susan Galbraith, EVP of AstraZeneca’s Oncology R&D, emphasized that the data highlight datopotamab deruxtecan’s potential to improve outcomes in patients whose disease has become resistant to current treatments, including those with various EGFR mutations. The forthcoming trial in patients with TROP2-QCS biomarker-positive tumors is another critical step in exploring its full potential.
Patients in the pooled analysis had received a median of three prior lines of treatment, with 82% having been previously treated with osimertinib. A variety of EGFR mutations were present, including exon 19 del, exon 21 L858R, and exon 20 T790M, among others.
Summary of Pooled Results:
| Measure | EGFR-mutated Pool (n=117) | Prior Osimertinib (n=96) |
|---|---|---|
| ORR (%) | 42.7% [33.6-52.2] | 44.8% [34.6-55.3] |
| CR (%) | 4.3% | 4.2% |
| PR (%) | 38.5% | 40.6% |
| SD (%) | 41.0% | 38.5% |
| Median DOR (months) | 7.0 [4.2-9.8] | 6.9 [4.2-9.8] |
| DCR (%) | 86.3% [78.7-92.0] | 85.4% [76.7-91.8] |
| Median PFS (months) | 5.8 [5.4-8.2] | 5.7 [5.4-7.9] |
| Median OS (months) | 15.6 [13.1-19.0] | 14.7 [13.0-18.3] |
About TROPION-Lung05 and TROPION-Lung01
TROPION-Lung05 is a phase 2 trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with advanced NSCLC who have progressed on prior therapies. It enrolled 137 patients globally. TROPION-Lung01 is a phase 3 trial comparing datopotamab deruxtecan to docetaxel in patients with advanced NSCLC.
About Datopotamab Deruxtecan
Datopotamab deruxtecan is an investigational TROP2-directed ADC, developed using Daiichi Sankyo’s DXd ADC technology. It is part of a broad clinical program exploring its potential in NSCLC, breast cancer, and other cancers.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca have a global collaboration to develop and commercialize datopotamab deruxtecan and other ADCs, focusing on advancing cancer care worldwide.
About Advanced Non-Small Cell Lung Cancer
Lung cancer is the most common cancer globally, with EGFR mutations found in a significant portion of NSCLC cases, particularly in Asia. While EGFR TKIs have improved first-line treatment outcomes, many patients eventually develop resistance and require new treatment options. Datopotamab deruxtecan offers a promising approach in this setting.
