Zidesamtinib Delivers 94% Response Rate in TKI-Naive ROS1-Positive NSCLC, Supporting First-Line Filing
核心洞察
In the Phase I/II ARROS-1 trial, zidesamtinib produced a 94% objective response rate in 94 TKI-naive patients with advanced ROS1-positive NSCLC (搜索) by blinded independent central review.
Among 10 evaluable patients with CNS metastases, intracranial objective response rate reached 100%, including a 70% intracranial complete response rate.
GSK plans a supplemental new drug application to the FDA later this year seeking first-line approval, after Jideytro (搜索)'s July approval in previously treated disease.
Zidesamtinib (marketed as Jideytro (搜索)) achieved a 94% objective response rate in tyrosine kinase inhibitor (TKI)-naive patients with advanced or metastatic ROS1 (搜索)-positive non-small cell lung cancer (搜索) (NSCLC), according to new data from the global Phase I/II ARROS-1 trial presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul, Republic of Korea.
Among 94 efficacy-evaluable TKI-naive patients, the objective response rate by blinded independent central review was 94% (88 of 94 patients). The nine-month duration-of-response rate was 94%, and the 12-month duration-of-response rate was 86%. GSK reported that 15% of patients achieved a complete response after a median follow-up of 15.2 months, and that 90% of patients remained progression-free at 12 months, with median progression-free survival not yet reached.
Intracranial Activity in CNS Metastases
Zidesamtinib also demonstrated substantial intracranial activity. Among 10 evaluable patients with central nervous system metastases, the intracranial objective response rate was 100%, including a 70% intracranial complete response rate. The nine-month intracranial duration-of-response rate was 100%, and the 12-month rate was 78%. Approximately 70% of patients with measurable brain metastases achieved complete clearance of detectable brain tumors.
The brain-penetrant profile is clinically relevant because ROS1 (搜索)-positive lung cancer (搜索) frequently spreads to the central nervous system, and the drug's selective design is intended to reduce some of the neurological and gastrointestinal side effects associated with earlier agents.
Trial Design and Population
The global, single-arm, first-in-human ARROS-1 trial included a Phase II cohort of patients with locally advanced or metastatic ROS1-positive NSCLC (搜索) who were naive to TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy was permitted. Patients received zidesamtinib 100 mg once daily.
Across all lines of therapy, 532 patients with ROS1-positive NSCLC (搜索) received zidesamtinib 100 mg once daily, including 183 who were TKI-naive. The study population was geographically diverse, with 35% of patients enrolled in the Asia-Pacific region, 33% in Europe and 32% in North America.
Safety Profile
The most common treatment-related adverse events occurring in at least 15% of patients were peripheral edema (34%), increased weight (18%), increased blood creatine phosphokinase (18%), dysgeusia (17%) and increased aspartate aminotransferase (15%). Treatment-related adverse events led to dose reductions in 11% of patients and treatment discontinuation in 1%.
"Zidesamtinib demonstrated clinically meaningful activity in TKI-naive patients with ROS1-positive NSCLC (搜索), with a safety profile consistent with previous reports and low rates of dose reduction and discontinuation. The findings support continued investigation of zidesamtinib in earlier lines of therapy," said Alexander Drilon, M.D., of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York City.
Regulatory Path and Commercial Context
Zidesamtinib is a next-generation, highly selective ROS1 (搜索) inhibitor already approved for previously treated ROS1-positive NSCLC (搜索); the FDA granted approval in July for previously treated advanced lung cancer (搜索) with a specific mutation, marking GSK's first approval in lung cancer. GSK said the ARROS-1 data will be part of the package it plans to submit to the FDA through a supplemental new drug application later this year to move the medicine into first-line treatment.
The drug entered GSK's oncology portfolio as a late-stage candidate through the company's $10.6 billion acquisition of Nuvalent in July. GSK's head of oncology research and development, Hesham Abdullah, said on a call with reporters that the company is on track with moving its plans forward given the data in hand. Management expects the Nuvalent acquisition to contribute to sales and core operating profit from 2027.
The Nuvalent deal also brought neladalkib, an investigational ALK (搜索) inhibitor currently under FDA review with a PDUFA target date of Nov. 27, 2026, and NVL-330, a HER2 (搜索)-targeted therapy in Phase I evaluation for HER2-altered NSCLC. GSK described the two lead drugs as potential multi-blockbusters when the deal was announced.
Separately, GSK reported that Ris-Rez (搜索), an antibody-drug conjugate targeting B7-H3 (搜索) licensed from Hansoh (搜索), reduced the risk of death by 54% versus standard treatment in a Chinese Phase III study of relapsed small-cell lung cancer (搜索), with median survival reaching 18.5 months compared with 10.3 months. GSK still needs its own global Phase III program to confirm that performance in the populations required for major Western approvals.
The commercial rationale for earlier-line use is that a therapy approved only after previous drugs have failed addresses a narrower patient population, while first-line use opens access to patients from the beginning of treatment and potentially keeps them on therapy for longer. GSK shares rose around 3.6% on September 14 following the data release.