First-in-Human Trial Lays the Foundation for Commercialization

TROPION-PanTumor01 is the first global Phase 1 trial of Datroway (datopotamab deruxtecan-dlnk), developed by Daiichi Sankyo. The drug is an antibody-drug conjugate (ADC) that combines an antibody recognizing the tumor cell surface antigen TROP2 with the topoisomerase I inhibitor DXd. The open, multi-center trial, which began in January 2018, consists of dose-escalation and expansion phases, enrolling 890 patients with a target completion date of January 2027. Initially designed to explore safety, the trial has since expanded into a platform validation study, establishing the 6 mg/kg every three weeks as the dose for subsequent Phase 3 trials and regulatory approval.

Balancing Clinical Signals and Safety

Among 159 patients with progressive non-small cell lung cancer (NSCLC) after standard therapy, the independent central review objective response rate (ORR) was 21–25% across dose groups, with a disease control rate (DCR) of 67–80%, and a median progression-free survival (mPFS) of 4.3–8.2 months. In 34 evaluable patients with actionable genomic alterations, a confirmed ORR of 35% and a median duration of response of 9.5 months were observed. These signals, observed in a TROP2 expression-unselected, refractory patient population, provided the basis for subsequent NSCLC development. Meanwhile, stomatitis, nausea, ocular toxicity, and interstitial lung disease (ILD)/pneumonia remain key variables for treatment persistence and risk management, prompting the inclusion of sub-studies on steroid and bis-steroid oral rinse prophylaxis.

Development Pathway Leading to Approval

Following this Phase 1 trial, Datroway advanced into later-stage clinical trials, including TROPION-Lung01, Lung05, and TROPION-Breast01, and has already reached the commercial stage. The Japanese Ministry of Health, Labour and Welfare approved it for HR-positive, HER2-negative advanced breast cancer on December 27, 2024, while the U.S. FDA granted approval on January 17, 2025. The European Union also approved the indication in 2025. On June 23, 2025, the FDA granted accelerated approval for EGFR-mutated advanced NSCLC patients who had previously received EGFR-targeted therapy and platinum-based chemotherapy, based on an integrated analysis of 114 patients from Lung05 and Lung01. Thus, PanTumor01 has transitioned from a simple safety trial to an early clinical asset supporting accelerated approval for lung cancer and expansion into multiple tumor types.

Market, Competitive, and Partnership Implications

The global NSCLC treatment market is projected to grow from $21.5 billion in 2024 to $43.9 billion by 2030. In the EGFR-mutated patient segment, Tagrisso (osimertinib, EGFR), platinum-based chemotherapy, and docetaxel are key comparators in treatment pathways. In the TROP2 ADC competitive landscape, Gilead Sciences' (GILD) Trodelvy (sacituzumab govitecan-hziy) has established a first-mover position in breast cancer, while in lung cancer, Datroway must compete with chemotherapy, immune checkpoint inhibitors, and other targeted ADCs in terms of efficacy, ILD, and stomatitis management. AstraZeneca (AZN) entered into a global co-development and commercialization agreement with Daiichi Sankyo in July 2020, setting an upfront payment of $1 billion and conditional milestone payments of $5 billion. In Japan, Daiichi Sankyo holds exclusivity, while in other regions, development costs and profits are equally shared between the two companies, directly linking clinical success to both companies' financial performance and the value of the DXd platform.