Datopotamab Deruxtecan Demonstrated Meaningful Clinical Activity in Patients with Previously Treated Advanced EGFR- Mutated Non-Small Cell Lung Cancer in TROPION-Lung05 and TROPION-Lung01 Pooled Analysis- Daiichi Sankyo

Datopotamab deruxtecan demonstrated a confirmed objective response rate (ORR) of 42.7% (95% confidence interval [CI]: 33.6-52.2) in a pooled analysis of 117 patients with EGFR-mutated NSCLC from the TROPION-Lung05 (n=78) and TROPION-Lung01 (n=39) trials, as assessed by blinded independent central review (BICR). Five (4.3%) complete responses (CRs), 45 (38.5%) partial responses (PRs) and 48 (41.0%) cases of stable disease (SD) were observed. The median duration of response (DOR) was 7.0 months (95% CI: 4.2-9.8) and the disease control rate (DCR) was 86.3% (95% CI: 78.7-92.0). Median progression-free survival (PFS) was 5.8 months (95% CI: 5.4-8.2) and median overall survival (OS) was 15.6 months (95% CI: 13.1-19.0).

Results in patients previously treated with osimertinib were similar to the overall pooled population. In 96 patients previously treated with osimertinib, a confirmed ORR of 44.8% (95% CI: 34.6-55.3), as assessed by BICR was seen. Four (4.2%) CRs, 39 (40.6%) PRs and 37 (38.5%) cases of SD were observed. The median DOR was 6.9 months (95% CI: 4.2-9.8) and the DCR was 85.4% (95% CI: 76.7-91.8). Median PFS was 5.7 months (95% CI: 5.4-7.9) and median OS was 14.7 months (95% CI: 13.0-18.3). 

The safety profile of datopotamab deruxtecan was consistent with previous reports from the TROPION-Lung05 and TROPION-Lung01 trials, with no new safety concerns identified. The most common treatment-related adverse events (TRAEs) of any grade were stomatitis (59%), alopecia (49%), nausea (46%), fatigue (18%), decreased appetite (16%), constipation (15%), vomiting (12%), rash (11%) and pruritus (10%). Grade 3 or higher TRAEs occurred in 23% of patients. Adverse events of special interest (AESI) of any grade were stomatitis, ocular surface events and adjudicated drug-related interstitial lung disease. No grade 4 or 5 stomatitis, ocular surface events or adjudicated drug-related ILD events occurred.

“Results of this pooled analysis show the potential for datopotamab deruxtecan in patients with EGFR-mutated non-small cell lung cancer with disease progression following multiple lines of prior treatment in the metastatic setting,” said Dr. Ken Takeshita, Global Head, R&D, Daiichi Sankyo. “The data from the TROPION-Lung05 and TROPION-Lung01 trials support our recent regulatory submission in the U.S.and highlight the potential of datopotamab deruxtecan to become a new treatment option for this patient population.”

" These results show that datopotamab deruxtecan can improve outcomes for patients with EGFR-mutated non-small cell lung cancer whose disease has become resistant to current treatments and that it has potential to do so in patients harboring a range of EGFR mutations,” said Dr. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca. “These data, as well as our forthcoming trial in patients with TROP2-QCS biomarker-positive tumors, mark critical steps in our effort to follow the science and understand the full potential of datopotamab deruxtecan in later-line lung cancer settings.”

Patients in the pooled analysis received a median of three prior lines of treatment in the metastatic setting (range, 1-5).Up to 82%  of patients were previously treated with osimertinib, including 40.2% in the first line and 29.1% in the second line.  In the pooled population, a range of EGFR mutations was observed, including exon 19 del, exon 21 L858R, exon 20 T790M, exon 18 G719X, exon 21 L861Q, exon 20 ins and exon 20 C797S.