Results from the international Phase 1/2 clinical trial ARROS-1 show promising outcomes with zidesamtinib, a novel ROS1 selective inhibitor under investigation, in patients with advanced non-small cell lung cancer (NSCLC) harboring ROS1 alterations who had previously been treated with tyrosine kinase inhibitors (TKIs).
The study data, in which Dr. Enriqueta Felip, Head of the Medical Oncology Section at Vall d’Hebron University Hospital and Head of the Thoracic Tumors Group at VHIO, participated, were presented today in the Presidential Symposium of the World Conference on Lung Cancer (WCLC 2025), held September 6–9 in Barcelona and organized by the International Association for the Study of Lung Cancer (IASLC).
“Research into new targeted therapies is essential to provide better options for patients with ROS1-driven tumors, which often develop resistance to currently available treatments. The results presented with zidesamtinib represent a major step forward in this area,” said Dr. Felip.
Promising response rates
The ARROS-1 trial enrolled 432 patients with NSCLC and other solid tumors harboring ROS1 rearrangements.
Among 117 patients previously treated with one or more lines of TKI therapy with or without chemotherapy, the objective response rate (ORR) was 44%, with estimated durability of response at 78% at 12 months and 62% at 18 months. In the 55 patients who had received only one prior line of TKI therapy, with or without chemotherapy, the ORR was 51%, with estimated durability of response of 93% at both 12 and 18 months.
“In the group of patients who were TKI-naïve, the objective response rate reached 89%, which underscores the need to continue investigating this experimental therapy in earlier settings, including as a potential first-line treatment for patients whose tumors harbor ROS1 rearrangements,” noted Dr. Felip.
Zidesamtinib has been designed to overcome resistance to currently available ROS1 inhibitors, including specific mutations such as G2032R, and to penetrate the blood–brain barrier, which may be especially relevant for patients with brain metastases. In addition, its selectivity helps avoid adverse events associated with other, less specific inhibitors.
“Between 1% and 2% of NSCLC patients present ROS1 rearrangements. The ARROS-1 results open the door to offering new treatment options for pretreated patients, including those with brain metastases or emerging resistance mutations,” added Dr. Felip.
The ARROS-1 (Phase 1/2) global, multicenter trial remains ongoing with registrational intent in both pretreated and treatment-naïve patients.
References
Session details
WLCC 2025 Barcelona
Sep 7 2025 8:15AM – 10:30AM
Presidential Symposium
Plenary Hall
PL02.10 Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+ NSCLC
A.E. Drilon1, B.C. Cho2, J.J. Lin3, B.J. Solomon4, C-C. Lin5, A.J. de Langen6, E. Felip7, J.W. Neal8, S.V. Liu9, R.A. Soo10, S. Kao11, J. Wolf12, G. Liu13, C.S. Baik14, C. Dooms15, M. Nagasaka16, A.J. van der Wekken17, D.R. Camidge18, T. Yoshida19, C-C. Lin20, G-C. Chang21, M-J. Ahn22, J.R. Bauman23, S. Gadgeel24, A. Calles25, E. Pons-Tostivint26, D.S.W. Tan27, M. Johnson28, C. Bennati29, G. Spitaleri30, S. Waqar31, S. Popat32, H. Hayashi33, D. Haggstrom34, M. Samant35, J. Shen35, V.A. Upadhyay35, B. Besse36
Speaker: Alexander Drilon Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center,
