Zidesamtinib

Having recently entered the lung cancer field via the FDA approval of its newly-acquired ROS1 selective inhibitor Jideytro (zidesamtinib), GSK is pushing forward with plans to expand use to include first-line treatment based on new data presented over the weekend at the World Conference on Lung Cancer (WCLC).Jideytro gained FDA clearance in July for adults with locally advanced or metastatic ROS1-positive non–small-cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor. The decision was based on results from the Phase I/II ARROS-1 trial, in which Jideytro achieved an objective response rate (ORR) of 44% in previously treated patients, rising to 51% in those who received only one prior ROS1 inhibitor.New findings from the study presented at the WCLC showed that in a cohort of patients who were naïve to ROS1 tyrosine kinase inhibitor (TKI) therapy, Jideytro led to an ORR of 94% after 15.2 months of follow-up, including a 15% complete response rate. Results showed that 90% of participants were progression-free at 12 months, with median progression-free survival (PFS) yet to be reached."Today’s results show a combination of high response rates and a tolerability profile that helped most patients stay on treatment," said Hesham Abdullah, GSK's global head of oncology, R&D.In patients naïve to ROS1 TKI therapy, the most common treatment-related adverse events (TRAEs) were peripheral oedema, weight increase, blood creatine phosphokinase increase, dysgeusia and AST enzyme increase, although the majority were low grade. GSK noted that TRAEs led to dose reductions in 11% of patients and discontinuations in 1%.The drugmaker, which gained Jideytro through the $10.6-billion purchase of Nuvalent, plans to seek expanded FDA approval before the end of 2026. Meanwhile, a second asset that formed part of the deal, the ALK-selective inhibitor neladalkib, is nearing a Nov. 27 decision deadline for ALK-positive NSCLC (see – Spotlight On: The ASCO moment that sealed GSK's biggest deal in years).

GSK is advancing its inaugural lung cancer asset, Jideytro, toward a landmark first-line FDA approval, aided by an unprecedented complete response rate. In a quick return for GSK’s $10.6 billion acquisition of Nuvalent, an early FDA nod in July has made Jideytro GSK’s first commercial lung cancer drug, with a label covering advanced ROS1-positive non-small cell lung cancer following treatment with a prior ROS1 tyrosine kinase inhibitor (TKI). Now, the company is gunning for an expansion into the TKI-naïve population. That plan is supported by new data from the single-arm Arros-1 trial. Among 94 efficacy-evaluable TKI-naïve patients, Jideytro triggered an objective response in 88 patients (94%), according to data presented at the 2026 World Conference on Lung Cancer in Seoul. These patients were allowed to have received up to one prior line of chemotherapy with or without immunotherapy before entering the study. In a data point that GSK’s oncology R&D chief Hesham Abdullah, M.D., described as “quite dramatic,” Jideytro led to a 15% (14/94) complete response rate in these ROS1 TKI-naïve NSCLC patients. As Abdullah noted, the rate is more than double what other ROS1 inhibitors have shown in the past. Ibtrozi, another newer-generation ROS1 inhibitor developed by Nuvation Bio, previously recorded 5% and 7% complete response rates in two single-arm trials in TKI-naïve patients. At 12 months, 86% of responders to Jideytro were still in remission. That 12-month duration of response rate was also numerically better than Ibtrozi’s, which reached 72% and 63% between Nuvation’s two studies. With a data cut-off in April and a median follow-up of 15.2 months, the median duration of response was not yet reached for Jideytro. The 94-person subgroup represents TKI-naïve patients who have been followed for at least nine months. Both Jideytro and Ibtrozi aim to improve on older ROS1 inhibitors by exerting higher selectivity for ROS1 and the ability to penetrate the blood-brain barrier. On that latter point, Jideytro significantly shrank tumors in all 10 evaluable patients (100%) with central nervous system metastases, including a 70% intracranial complete response rate. By comparison, Ibtrozi’s label shows intracranial responses among 11 of 15 TKI-naïve patients (73%) who had CNS metastases at baseline across its two trials. GSK is on track to use the latest Arros-1 data to support an FDA filing in TKI-naïve ROS1 NSCLC this year, Abdullah told reporters during a media briefing. In buying Jideytro—along with near-market ALK inhibitor neladalkib—as part of its Nuvalent acquisition, GSK has said the ROS1 inhibitor holds multi-blockbuster sales potential. ROS1 mutation is rare, occurring in only about 1% to 2% of all NSCLC cases. But compared with the larger NSCLC population without actionable genetic biomarkers who typically receive PD-1 inhibitors and chemo as first-line treatment, the duration of treatment for ROS1 patients is much longer, Abdullah noted. While the median progression-free period for the broader first-line NSCLC population is about nine months to 11 months, ROS1 patients could stay on treatment without disease worsening for years, potentially beyond 44 months, Abdullah said. Nevertheless, existing ROS1 inhibitors marketed by the likes of Bristol Myers Squibb, Pfizer and Roche have performed poorly commercially partly because of toxicity. In terms of safety, among 532 ROS1-positive NSCLC patients who received Jideytro for any line of therapy in Arros-1, treatment-related adverse events so far led to dose reductions in 11% of patients and discontinuation in 1% of participants. Peripheral edema, or the buildup of excess fluid in the tissues of the limbs, and liver enzyme elevations are among the most common treatment-related adverse events, although very few have reached grade 3 or above. Jideytro “demonstrated clinically meaningful activity in TKI-naïve patients with ROS1-positive NSCLC, with a safety profile consistent with previous reports and low rates of dose reduction and discontinuation,” Alexander Drilon, M.D., of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, who led the Arros-1 trial, said in a statement provided by WCLC. “The findings support continued investigation of [Jideytro] in earlier lines of therapy.” Even with strong clinical data, GSK’s commercial team has its work cut out for it. Despite intracranial activity and enhanced tolerability from higher ROS1 selectivity, Nuvation’s Ibtrozi pulled in a modest $23.2 million in second-quarter sales. On the bright side, sales are expected to gain momentum in the longer term as patients accumulate on extended treatment durations.