Repotrectinib

In a landmark moment for its oncology ambitions, GSK has secured FDA approval for Jideytro (zidesamtinib) as the first commercial lung cancer drug in the company’s history. The milestone was made possible by GSK’s recent acquisition of Nuvalent for $10.6 billion. The approval for Jideytro comes just a week after the British pharma closed the deal and about two months ahead of the FDA’s target decision date of Sept. 18. The green light allows Jideytro to treat adult patients with advanced ROS1-positive non-small cell lung cancer who received a prior ROS1 inhibitor. “The rapid progression of Jideytro from development to approval reflects both the strength of the underlying science and the urgent need for additional effective and tolerable treatments for ROS1-positive lung cancer,” GSK’s chief scientific officer, Tony Wood, said in a July 22 statement. By GSK’s estimate, about 50,000 new cases of ROS1-positive NSCLC are diagnosed each year worldwide, mostly among non-smokers in their 40s and 50s who could stay on treatment for several years. GSK has suggested that Jideytro holds “multi-blockbuster potential,” an ambitious projection considering none of the existing ROS1 NSCLC drugs—by Pfizer, Roche, Bristol Myers Squibb and most recently, Nuvation Bio—have come close to that target. Jideytro differentiates itself from earlier therapies such as Pfizer’s Xalkori and BMS’ Augtyro through its unique molecular design. Nuvalent designed Jideytro to overcome treatment-emergent ROS1 mutations while sparing the structurally related TRK family, thereby preventing off-target toxicities. It features robust central nervous system penetration to tackle brain metastases, a common complication in ROS1-positive NSCLC. In the single-arm Arros-1 phase 1/2 clinical trial, Jideytro booked an objective response rate of 44% in 117 patients with ROS1 inhibitor-pretreated NSCLC. In terms of duration of response, 82% and 69% of responders remained in remission at six months and 12 months, respectively. Among 50 patients who had measurable brain metastases, responses were observed in 48% of patients, including 22% with a complete response, according to the drug’s label. A 50% ORR rate was also recorded in the 42 patients who had ROS1 resistance mutations. Despite the strong data, GSK has a long ways to go before Jideytro could reach blockbuster status. One of its primary competitors is Ibtrozi (taletrectinib) by David Hung’s Nuvation Bio. Following a line-agnostic FDA nod for ROS1-positive NSCLC in June 2025, Ibtrozi—which also features intracranial activity and TRK sparing— generated $18.5 million during the first quarter of 2026. The current Jideytro label only allows the GSK drug to be used in patients who received a prior ROS1 inhibitor. Responding to a Fierce inquiry, a GSK spokesperson pointed to Nuvalent’s previous comment that it would seek a first-line label expansion this year. At the 2026 American Society of Clinical Oncology annual meeting, Nuvalent also reported promising preliminary data for zidesamtinib in non-NSCLC solid tumors, indicating the drug may hold pan-tumor potential with a 40% ORR across 10 tumor types. Jideytro is the first product emerging from GSK’s Nuvalent acquisition. Neladalkib, a fourth-generation ALK inhibitor, could be next with an FDA target action date of Nov. 27, 2026, for advanced ALK-positive NSCLC. GSK has floated multi-blockbuster hopes for that drug, too. Beyond the Nuvalent assets, GSK is advancing risvutatug rezetecan (ris-rez), a B7-H3-targeted antibody-drug conjugate, in a phase 3 extensive-stage small-cell lung cancer study. The drug’s original developer, Hansoh Pharma, just reported a phase 3 win in SCLC in China.

GSK could see speedy returns from its $10.6-billion buy of Nuvalent, thanks to an FDA nod Wednesday for the first programme from the takeout, Jideytro (zidesamtinib). The US regulator approved the ROS1 selective inhibitor for adults with locally advanced or metastatic ROS1-positive non–small-cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor. The purchase, announced in June and officially closed last week, handed GSK a pair of lung cancer treatments already under review at the FDA. Jideytro's clearance came about two months ahead of its Sept. 18 PDUFA date, while the second asset, 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)."The rapid progression of Jideytro from development to approval reflects both the strength of the underlying science and the urgent need for additional effective and tolerable treatments for ROS1-positive lung cancer," said GSK's Chief Scientific Officer Tony Wood. Analysts have projected nearly $2 billion in peak annual sales for the drug, a next-generation blood-brain-barrier–penetrant inhibitor designed to broadly address ROS1 resistance mutations while remaining highly target-selective. However, to reach that sales goal, Jideytro will have to overtake several competitors in the ROS1-positive NSCLC space, including Roche's Rozlytrek (entrectinib), Bristol Myers Squibb's Augtyro (repotrectinib) and Nuvation's Ibtrozi (taletrectinib) — though analysts at Jefferies have argued that the candidate's improved tolerability, as well as activity against resistance mutations and in the central nervous system, could lift provide the product with a differentiating edge (see – Spotlight On: Three things to watch at GSK). Response rate resultsJideytro was approved based on results from the Phase I/II ARROS-1 trial, which enrolled patients with previously treated, advanced ROS1-positive NSCLC. The therapy achieved an objective response rate (ORR) of 44% in the overall 117-patient population, while a subgroup of 55 patients who had received only one prior ROS1 inhibitor experienced an ORR of 51%. In patients treated with two or more prior ROS1 inhibitors, the ORR was 38%. In addition, Jideytro demonstrated a 69% duration of response rate at 12 months. A pooled safety analysis comprising 446 participants showed that the therapy's most common adverse reactions — those occurring in 15% or more of patients — were oedema, peripheral neuropathy, constipation, fatigue and dyspnoea.