### Datopotamab Deruxtecan Impresses in Combination Study of Patients with Previously Treated Advanced or Metastatic EGFR-Mutated NSCLC
An analysis combining data from the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 studies has shown that datopotamab deruxtecan (Dato-DXd) leads to notable tumor shrinkage in individuals who have received earlier treatment for advanced or spreading EGFR-mutant non-small cell lung cancer (NSCLC). These findings, together with progression-free and overall survival metrics, were shared during the late-breaking session (LBA7) at the 2024 ESMO Asia (#ESMOAsia24) Congress.
Datopotamab deruxtecan is a specialized TROP2 targeting DXd antibody-drug conjugate (ADC) developed by Daiichi Sankyo and co-developed with AstraZeneca.
In 117 patients with EGFR-mutant NSCLC from TROPION-Lung05 (n=78) and TROPION-Lung01 (n=39), independently reviewed data confirmed an objective response rate (ORR) of 42.7% (95% confidence interval [CI]: 33.6-52.2). Out of these, five (4.3%) showed complete responses (CRs), 45 (38.5%) had partial responses (PRs), and 48 (41.0%) maintained stable disease (SD). The median response span was 7.0 months (95% CI: 4.2-9.8), with an 86.3% disease control rate (DCR) (95% CI: 78.7-92.0). Subjects experienced a median progression-free survival (PFS) of 5.8 months (95% CI: 5.4-8.2) and median overall survival (OS) of 15.6 months (95% CI: 13.1-19.0).
“First-line EGFR tyrosine kinase inhibitors have provided considerable strides for those with advanced EGFR-mutant non-small cell lung cancer, but many encounter disease progression,” remarked Myung-Ju Ahn, MD, PhD, Professor of Hematology-Oncology, Samsung Medical Center. “The results indicate that datopotamab deruxtecan could present a new option for patients with pre-treated metastatic cancer.”
For patients who had prior treatment with osimertinib, responses mirrored those of the general pooled group. Among 96 previously treated with osimertinib, a verified ORR of 44.8% (95% CI: 34.6-55.3) was noted. This group had four (4.2%) complete responses (CRs), 39 (40.6%) partial responses (PRs), and 37 (38.5%) stable diseases (SD). Their median response duration was 6.9 months (95% CI: 4.2-9.8), and their DCR was 85.4% (95% CI: 76.7-91.8). The median PFS was recorded at 5.7 months (95% CI: 5.4-7.9), and the median OS was 14.7 months (95% CI: 13.0-18.3).
Safety reports aligned with previous observations from TROPION-Lung05 and TROPION-Lung01, without new safety alerts. Frequent adverse events (TRAEs) involved stomatitis (59%), hair loss (49%), nausea (46%), fatigue (18%), decreased appetite (16%), and others. Severe events of Grade 3 or higher occurred in 23% of participants, with no Grade 4 or 5 cases of particular interest such as ILD.
“This analysis illustrates datopotamab deruxtecan’s potential post-multiple previous lines of therapy,” noted Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo. “It underpins our recent US regulatory submission and emphasizes its potential to emerge as a fresh treatment choice.”
Susan Galbraith, MBBChir, PhD, AstraZeneca’s EVP of Oncology R&D, added, “These findings demonstrate how datopotamab deruxtecan can improve outcomes for patients who have exhausted standard therapies, maintaining promise across different EGFR mutations.”
Most patients in this pooled data analysis had previously undergone three lines of therapy (range 1-5) in the metastatic phase, with osimertinib having been administered to 82%, including the initial and second lines. Various EGFR mutations were documented, such as exon 19 del and exon 21 L858R.
TROPION-Lung05 evaluates the effectiveness and safety of datopotamab deruxtecan in patients who have exhausted prior treatments including EGFR, ALK, ROS1, NTRK mutations, among others. The phase 3 TROPION-Lung01 contrasts its efficacy with docetaxel in similar patient groups, with endpoints such as PFS and OS among others.
A massive 2.5 million lung cancer cases were globally diagnosed in 2022, with non-small cell lung cancer comprising about 80%. While EGFR mutations primarily emerge in non-squamous tumors, current standard treatments aim to target these, though resistance eventually prompts alternate therapies. Datopotamab deruxtecan emerges as an investigational treatment in this field, showcasing a high clinical potential to meet previously unmet needs.