Jideytro (zidesamtinib) / Royalty, GSK - LARVOL DELTA

Zidesamtinib in TKI-naive Patients with Advanced/Metastatic ROS1+ NSCLC: ARROS-1 Efficacy and Safety Data (IASLC-WCLC 2026) - P1/2 | "The safety profile was consistent with previous reports, 1,2 with low rates of dose reductions and discontinuations. These data support continued investigation of zidesamtinib in earlier lines of therapy."

Clinical • First-in-human • Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ROS1

Phase I/II ARROS-1 study of zidesamtinib (NVL-520) in ROS1 fusion-positive solid tumours (ESMO 2024) - P1/2 | "Pts had a median of 3 (range: 1-11) prior anticancer therapies, including any ROS1 TKI (99%); lorlatinib (55%), repotrectinib (repo; 21%), or either (67%); ≥2 ROS1 TKIs (69%); and chemo (66%). Zidesamtinib demonstrated encouraging efficacy and durability in pts with pretreated ROS1+ NSCLC, including those who had exhausted available therapies, with ROS1 resistance mutations including G2032R, and/or with CNS mets. Safety was favorable and consistent with the highly ROS1-selective and TRK-sparing design. Ph 2 enrollment is ongoing with registrational intent in pts with TKI-naïve and pretreated ROS1+ NSCLC."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+ NSCLC (IASLC-WCLC 2025) - P1/2 | "50% of patients received ≥2 (range 1-4) prior ROS1 TKIs, of whom 93% had prior lorlatinib, repotrectinib, and/or taletrectinib. In this pivotal ROS1 TKI pre-treated data set, zidesamtinib demonstrated clinically meaningful activity and durability, including in patients with CNS disease and/or ROS1 G2032R-mutations, and/or in patients who had exhausted available options. Encouraging preliminary activity was also observed in TKI-naïve patients. Zidesamtinib's safety profile was consistent with its highly ROS1-selective, TRK-sparing design."

Clinical • Metastases • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Solid Tumor • ROS1

Safety and preliminary clinical activity of NVL-520, a highly selective ROS1 inhibitor, in patients with advanced ROS1 fusion-positive solid tumors (AACR-NCI-EORTC 2022) - P1/2 | "Rationally designed ROS1 tyrosine kinase inhibitors (TKIs) that surpass the limitations of FDA/EMA-approved (crizotinib/entrectinib) or other investigational agents are a medical need. The novel ROS1 TKI NVL-520 is highly selective and designed to avoid the neurologic toxicities associated with ROS1 TKIs that concurrently inhibit TRK (entrectinib/repotrectinib/taletrectinib)...Patients received a median of 3 (range: 1-9) prior anticancer therapies, including any ROS1 TKI (100%); investigational ROS1 TKI (85%, including lorlatinib in 55%, repotrectinib in 40%); ≥2 ROS1 TKIs (75%); any chemotherapy (80%); ≥2 lines of chemotherapy (50%)... NVL-520 has been well-tolerated up to 100 mg daily with favorable pharmacokinetics. Activity has been demonstrated in heavily pretreated patients (of whom 70% received ≥2 prior ROS1 TKIs plus chemotherapy), including those with brain metastases and the G2032R mutation."

Clinical • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ROS1

New results from the global Phase I/II ARROS-1 trial showed clinically meaningful activity with zidesamtinib in patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who had not previously received a tyrosine kinase inhibitor (TKI) (Mirage News) - "The findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC). 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%. 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%."

P1/2 data • Non Small Cell Lung Cancer

GSK prepares frontline FDA bid for Jideytro, its first lung cancer drug (Fierce Pharma) - "That plan is supported by new data from the single-arm Arros-1 trial....GSK is on track to use the latest Arros-1 data to support an FDA filing in TKI-naïve ROS1 NSCLC this year..."

FDA filing • Non Small Cell Lung Cancer

Pivotal ARROS-1 efficacy and safety data: zidesamtinib in TKI pre-treated patients with advanced/metastatic ROS1+ NSCLC (JADPRO 2025) - "BACKGROUND • Zidesamtinib is an investigational ROS1 TKI designed to be highly selective, have activity against diverse ROS1 fusions and ROS1 resistance mutations, be brain-penetrant, and avoid TRK inhibition • ARROS-1 is a global, single-arm, first-in-human Phase 1/2 clinical trial of zidesamtinib in advanced ROS1-positive (ROS1+) NSCLC and other solid tumors • Pivotal data for TKI pre-treated ROS1+ NSCLC and preliminary data for TKI-naïve ROS1+ NSCLC are presented ARROS-1 STUDY DESIGN & POPULATIONS • As of the data cut-off date of March 21, 2023, 514 patients with any ROS1+ solid tumor had been enrolled across Phase 1 and 2 – The safety population included 432 patients with advanced ROS1+ NSCLC who received zidesamtinib 100 mg QD – The efficacy population included 117 ROS1 TKI pre-treated patients with measurable disease by BICR and ≥ 6 months duration of response follow-up – The TKI-naïve cohort included 35 patients with measurable disease by BICR..."

Clinical • Metastases • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ROS1

Zidesamtinib (Jideytro®): a new selective, brain-penetrant ROS1 inhibitor approved for the treatment of ROS1-positive non-small cell lung cancer. (PubMed, Med Chem Res) - "Data from the ARROS-1 phase 1/2 trial demonstrated durable clinical efficacy and manageable safety in previously treated ROS1-positive NSCLC, including patients with CNS metastases and G2032R resistance. These results led to its accelerated FDA approval on July 22, 2026, for patients previously treated with a ROS1-targeted tyrosine kinase inhibitor."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zidesamtinib in patients with ROS1+ NSCLC previously treated with repotrectinib or taletrectinib (AACR 2026) - P1/2 | "The meaningful clinical activity presented here for zidesamtinib, including in pts with CNS disease and ROS1 G2032R resistance mutation, indicates that many ROS1+ NSCLCs remain ROS1-dependent beyond repotrectinib and taletrectinib."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

GSK completes $10.6 billion acquisition of Nuvalent (Investing.com) - "The transaction has an aggregate equity value of approximately $10.6 billion (£8.0 billion). Net of cash acquired, GSK’s aggregate investment totals approximately $9.4 billion (£7.1 billion). GSK completed a tender offer to acquire all of Nuvalent’s outstanding shares...The acquisition adds three lung cancer assets to GSK’s oncology portfolio. Zidesamtinib (NVL-520) and neladalkib (NVL-655)....The acquisition also includes NVL-330, which is in phase I development for HER2-altered NSCLC."

M&A • Non Small Cell Lung Cancer

GSK…announced the US Food and Drug Administration (FDA) has approved Jideytro (zidesamtinib), a ROS1 selective inhibitor, for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor (GSK Press Release) - "The approval comes ahead of the original target action date of 18 September 2026 and follows the FDA's Breakthrough Therapy and Orphan Drug Designations....The approval of Jideytro is based on results from the global single-arm ARROS-1 phase I/II clinical trial in patients with advanced or metastatic ROS1-positive NSCLC previously treated with a ROS1 inhibitor."

FDA approval • Non Small Cell Lung Cancer

Real-world treatment sequencing and survival in ROS1-Rearranged NSCLC across evolving treatment eras: Findings from the AURORA multi-centre registry (AURORA-ROS1). (PubMed, Lung Cancer) - "This multicentre real-world cohort describes longitudinal ROS1 management with evolving treatments. Favourable survival likely reflects reflex molecular testing, access to ROS1i, and high clinical trial enrolment."

HEOR • Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • ROS1

A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1) (clinicaltrials.gov) - P1/2 | N=359 | Recruiting | Sponsor: Nuvalent Inc. | N=247 ➔ 359

Enrollment change • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

GSK plc…announced that it has entered an agreement to acquire Nuvalent, Inc…a Boston-based clinical-stage biopharmaceutical company focused on creating precisely targeted oncology therapies, for $10.6 billion. (GSK Press Release) - "Both assets...are in review with target decision dates of 18 September 2026 for zidesamtinib and 27 November 2026 for neladalkib. Subject to FDA approval, they are expected to launch in 2026 and have multi-blockbuster potential. The third asset, NVL-330, is a potential best-in-class HER2 inhibitor currently in phase I trials for HER2-altered NSCLC...The acquisition provides GSK with immediate new sales growth opportunities, improving profit contributions from 2027, and a platform in lung cancer for rapid expansion with Ris-Rez, our B7-H3 targeted ADC in phase III clinical development...Under the terms of the merger agreement, GSK will commence a tender offer to acquire all of Nuvalent’s outstanding shares of Class A and Class B common stock at a purchase price of $124 per share in cash within 10 business days."

Launch US • Licensing / partnership • PDUFA • Non Small Cell Lung Cancer

Zidesamtinib efficacy and safety in patients with advanced ROS1-positive solid tumors other than NSCLC in the ARROS-1 study. (ASCO 2026) - P1/2 | "Zidesamtinib demonstrated encouraging activity in patients with diverse ROS1+ solid tumors, including those refractory to standard-of-care therapies. Safety was consistent with its ROS1-selective, TRK-sparing design. Enrollment is ongoing."

Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • ROS1

Preliminary Data for Zidesamtinib in Patients with Advanced ROS1-positive Solid Tumors Other than NSCLC from ARROS-1 Clinical Trial (PRNewswire) - "Preliminary data are reported for 15 response-evaluable patients enrolled across 10 solid tumor types outside of NSCLC in the Phase 1 and Phase 2 portions of the ARROS-1 clinical trial as of a data cutoff date of September 22, 2025. The majority (12/15) of patients received the recommended Phase 2 dose of 100 mg once daily. Patients were refractory to standard-of-care therapies (60%, 9/15) or were previously treated with a ROS1 TKI (40%, 6/15), and 73% (11/15) of patients had received prior chemotherapy....Enrollment is ongoing in the global Phase 2 cohort of the ARROS-1 trial for adult and adolescent patients with advanced ROS1-positive solid tumors other than NSCLC."

P1/2 data • Trial status • Non Small Cell Lung Cancer

"Nuvalent continues to advance commercial preparations ahead of an anticipated U.S. commercial launch of zidesamtinib in 2026, pending FDA review…Cash, cash equivalents and marketable securities were $1.3 billion as of March 31, 2026." (PRNewswire)

Launch US • Non Small Cell Lung Cancer

Zidesamtinib has differentiated preclinical brain penetrance and intracranial activity compared to other ROS1 inhibitors (AACR 2026) - "Tyrosine kinase inhibitors (TKIs) crizotinib, entrectinib, repotrectinib, and taletrectinib are FDA-approved for ROS1-positive non-small cell lung cancer. Zidesamtinib demonstrated improved preclinical brain penetrance and intracranial activity against ROS1 G2032R compared with taletrectinib and repotrectinib. Zidesamtinib's increased ROS1 G2032R potency and brain penetrance potentially underlie its differentiated intracranial activity in this preclinical setting."

Late-breaking abstract • Preclinical • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • CD74 • ROS1

A phase I study of the type II ROS1 TRK inhibitor ANS03 in ROS1 fusion-positive lung cancers (AACR 2026) - P1 | "Of the latter, six patients were pre-treated with 2-4 ROS1 TKIs including lorlatinib, repotrectinib, taletrectinib, and zidesamtinib. ANS03 had a manageable safety profile with a low incidence of neurotoxicity. In ROS1 fusion-positive NSCLCs, promising preliminary anti-tumor activity was achieved, including against ROS1 L2086F."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK • ROS1

ROS1-positive lung cancer treatment access gap across Canada - A call for equitable, patient-centered care (AACR 2026) - "Coverage policies, exceptional access programs, and clinical trial availability were systematically reviewed. While first-line agents (crizotinib, entrectinib) demonstrate universal coverage, profound inequities emerge in advanced-line therapy access in Canada...Next-generation TKIs addressing resistance mutations (repotrectinib, taletrectinib, zidesamtinib) and CNS disease remain accessible only through clinical trials... Canadian patients with ROS1-positive NSCLC face unjustifiable barriers to life-extending therapies beyond first-line treatment. The disconnect between therapeutic availability and public funding perpetuates health inequities and undermines precision oncology principles. Urgent policy reform is needed to: (1) establish consistent pan-Canadian coverage frameworks, (2) enable progression-based (not just intolerance-based) second-line access, (3) create pathways for third-line and resistance-directed therapy funding, and (4) accelerate approval timelines..."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Nuvalent to Present Pivotal Data from ALKOVE-1 Trial of Neladalkib in TKI Pre-treated Advanced ALK-positive NSCLC at the 2026 American Society of Clinical Oncology Annual Meeting (PRNewswire) - "Nuvalent, Inc....announced that pivotal data for neladalkib, an investigational ALK-selective inhibitor, in TKI pre-treated patients with advanced ALK-positive non-small cell lung cancer (NSCLC) from the global ALKOVE-1 Phase 1/2 clinical trial, in addition to preliminary data for TKI-naïve patients, will be presented during an oral presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting from May 29 – June 2, 2026, in Chicago...Additionally, preliminary data in patients with advanced ROS1-positive solid tumors outside of NSCLC from the global ARROS-1 Phase 1/2 clinical trial of zidesamtinib, an investigational ROS1-selective inhibitor, will be presented during a poster session."

P1/2 data • Non Small Cell Lung Cancer • Solid Tumor

New Clinical Data for Zidesamtinib in Subset of TKI Pre-treated Patients in ARROS-1 Trial (PRNewswire) - "New clinical...data for investigational candidate zidesamtinib presented at AACR Annual Meeting 2026....46 efficacy-evaluable patients had received prior repotrectinib, 19 had received prior taletrectinib, and 3 had previously received both; 85% (39/46) of repotrectinib-treated patients and 89% (17/19) of taletrectinib-treated patients had received ≥2 prior ROS1 TKIs; 63% (29/46) of repotrectinib-treated patients and 53% (10/53) of taletrectinib-treated patients had received prior chemotherapy; Active CNS disease was assessed by BICR in 46% (21/46) of repotrectinib-treated patients and 53% (10/19) of taletrectinib-treated patients at baseline..."

P1/2 data • Non Small Cell Lung Cancer

New…Preclinical Data for Investigational Candidate Zidesamtinib Presented at AACR Annual Meeting 2026 (PRNewswire) - "Among the three ROS1 TKIs, all of which have reported activity against the ROS1 G2032R mutation, zidesamtinib demonstrated: Highest cell permeability in MDCK-MDR1 cell lines and highest brain-to-plasma partitioning in rats, supporting zidesamtinib's potential for high brain penetrance; Most sustained intracranial efficacy in a mouse ROS1 G2032R brain tumor model, with all mice surviving to study end; and, Efficacy after progressive disease on earlier-line taletrectinib treatment in a mouse ROS1 G2032R brain tumor model."

Preclinical • Brain Cancer • CNS Tumor

Mutagenesis screens support potential best-in-class profile for selective, brain-penetrant, and TRK-sparing ROS1 inhibitor zidesamtinib (NVL-520) (AACR 2024) - "Tyrosine kinase inhibitors (TKIs) crizotinib, entrectinib, and repotrectinib have been approved for the treatment of ROS1-positive NSCLC. The screens did not reveal any novel ROS1 mutations that could confer resistance to NVL-520 at the RP2D. The broad preclinical activity against ROS1 and diverse ROS1 mutations, together with its brain penetrance and TRK-sparing design, suggests NVL-520 as a potential best-in-class ROS1 therapy."

Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD74 • ROS1

Crystal structure of drug-resistant ROS1 G2032R in complex with zidesamtinib, a clinical-stage ROS1 inhibitor with best-in-class potential (AACR 2025) - "Tyrosine kinase inhibitors (TKIs) crizotinib, entrectinib, and repotrectinib are FDA-approved for treatment of ROS1-positive NSCLC. Analysis of our ROS1 G2032R crystal structure and FEP modeling provide a structural explanation for how ROS1 G2032R impairs the binding of many ROS1 TKIs while maintaining high sensitivity to zidesamtinib. The data presented here, together with previously disclosed preclinical and clinical data, support our design of zidesamtinib as a differentiated ROS1 TKI with best-in-class potential for the treatment of ROS1-positive NSCLC."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK2 • ROS1