On May 21, 2026 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported 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, single-arm ALKOVE-1 Phase 1/2 clinical trial, and preliminary data in patients with advanced ROS1-positive solid tumors other than NSCLC from the global, single-arm ARROS-1 Phase 1/2 clinical trial of zidesamtinib, an investigational ROS1-selective inhibitor, to be presented at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from May 29 – June 2, 2026, in Chicago.
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"The pivotal data for neladalkib in TKI pre-treated patients with advanced ALK-positive NSCLC enabled our recent NDA submission to the FDA, and represent important progress toward our goal of offering a new treatment option for this patient population," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "Collectively, these data as well as preliminary data from the TKI-naïve cohort of our ALKOVE-1 study are supportive of further investigation of neladalkib in the global Phase 3 ALKAZAR trial of neladalkib compared to alectinib for TKI-naïve ALK-positive NSCLC, a critical step towards our ultimate goal of moving neladalkib up the treatment paradigm. We look forward to sharing these data with the medical community during an oral presentation at ASCO (Free ASCO Whitepaper), and are deeply grateful to the patients, caregivers, and investigators who have made this milestone possible."
"These data build on the consistent characterization of neladalkib across preclinical and Phase 1 investigations," said Jessica J. Lin, M.D., Program Director of Thoracic Medical Oncology at the Mass General Brigham Cancer Institute, Associate Professor of Medicine at Harvard Medical School, and presenting author. "The data support neladalkib’s potential to deliver on its design goals as an option for patients with ALK-positive NSCLC, including those whose disease progresses with brain metastases or resistance mutations, or who are unable to tolerate the currently available TKIs."
"We also continue to progress the development of zidesamtinib, our ROS1-selective inhibitor, and are pleased to share the preliminary activity observed in patients with ROS1-positive cancers other than NSCLC," said Darlene Noci, A.L.M., Chief Development Officer of Nuvalent. "These data highlight zidesamtinib’s potential for patients with ROS1-positive solid tumors outside of NSCLC, and we believe reinforce the importance of widespread genomic testing. We continue to enroll adult and adolescent TKI-naïve and TKI pre-treated patients with advanced ROS1-positive solid tumors outside of NSCLC in the global Phase 2 portion of our ARROS-1 study, and look forward to providing additional updates in the future."
Pivotal Data for Neladalkib in TKI Pre-treated Patients with Advanced ALK-positive NSCLC from ALKOVE-1 Clinical Trial
Title: ALKOVE-1: Efficacy and safety of neladalkib in patients with advanced ALK+ NSCLC
Presenting Author: Jessica J. Lin, M.D.1
Abstract Number: 8503
Oral Session Title: Lung Cancer—Non-Small Cell Metastatic
Presentation Date and Time: May 29, 2026, 1:00 PM-4:00 PM CDT
Location: Hall D2
The pivotal data to be presented, initially announced in November 2025, are from TKI pre-treated patients with advanced ALK-positive NSCLC treated with neladalkib in the global, registration-directed ALKOVE-1 Phase 1/2 clinical trial. In this population, neladalkib demonstrated encouraging overall activity, including intracranial responses, the ability to address key drivers of disease progression, and a generally well-tolerated safety profile consistent with its ALK-selective, TRK-sparing design. These data served as the foundation for the company’s New Drug Application (NDA) submission, announced in April 2026, to the U.S. Food and Drug Administration (FDA) for neladalkib in TKI pre-treated advanced ALK-positive NSCLC.
Preliminary Data for Zidesamtinib in Patients with Advanced ROS1-positive Solid Tumors Other than NSCLC from ARROS-1 Clinical Trial
Title: Zidesamtinib efficacy and safety in patients with advanced ROS1-positive solid tumors other than NSCLC in the ARROS-1 study
Presenting Author: Benjamin Solomon, M.D., Ph.D.2
Abstract Number: 3108
Poster Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Session Date and Time: May 30, 2026, 1:30 PM-4:30 PM CDT
Location: Hall A
Poster Board Number: 245
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.
Among all patients with advanced ROS1-positive solid tumors treated with zidesamtinib, an objective response rate of 40% (6/15) was observed, with responses seen for ROS1 TKI-naïve patients refractory to standard-of-care therapies, and for those who had received a prior ROS1 TKI. As of the data cutoff date, four of the six responders remained on treatment with zidesamtinib. Three case studies support zidesamtinib’s potential in a range of treatment settings:
Treatment ongoing for approximately 42 months with partial response in a TKI pre-treated patient with an inflammatory myofibroblastic tumor;
Treatment ongoing for approximately 13 months with partial response in a TKI-naïve patient with metastatic colorectal cancer previously treated with standard of care chemotherapy; and,
Treatment ongoing for approximately 19 months with partial response in a TKI-naïve patient with cholangiocarcinoma previously treated with standard of care chemotherapy.
Among these 15 patients, zidesamtinib was observed to be generally well-tolerated with only one dose reduction due to treatment-related adverse events (TRAEs) and no discontinuations due to TRAEs or treatment-emergent adverse events as of the data cutoff date. The preliminary overall safety profile was consistent with its ROS1-selective, TRK-sparing design, and with previously reported data.
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.
About Neladalkib
Neladalkib is an investigational, brain-penetrant, ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.
About Zidesamtinib
Zidesamtinib is an investigational, brain-penetrant, ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy.
Based on results for tyrosine kinase inhibitor (TKI) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) enrolled in the global, single-arm, registrational ARROS-1 Phase 1/2 clinical trial, the U.S. Food and Drug Administration (FDA) has accepted for filing Nuvalent’s NDA submission for zidesamtinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who received at least 1 prior ROS1 TKI. The application has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 18, 2026. Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic NSCLC who have been previously treated with 2 or more ROS1 TKIs and orphan drug designation for ROS1-positive NSCLC.
(Press release, Nuvalent, MAY 21, 2026, View Source [SID1234665958])