Nuvalent Presents Preliminary Data for Neladalkib in Advanced ALK-positive Solid Tumors Beyond NSCLC at ESMO 2025
Nuvalent (NASDAQ: NUVL) reported preliminary ALKOVE-1 data for neladalkib in advanced ALK-positive solid tumors beyond NSCLC with a data cutoff of August 7, 2025. Among 34 response-evaluable patients across 14 tumor types, overall objective response rate was 44% (15/34), including 9/13 ALK TKI‑naïve and 6/21 TKI‑pretreated patients. Most patients (32/34) received the recommended Phase 2 dose of 150 mg once daily.
Responses included durable case-study responses ongoing ~10–16 months and one confirmed intracranial complete response. Safety was described as generally well-tolerated with 8.8% dose reductions and no treatment-related discontinuations as of cutoff. Global Phase 2 enrollment continues; topline pivotal NSCLC data expected by end of 2025.
Nuvalent (NASDAQ: NUVL) ha riportato dati preliminari di ALKOVE-1 su neladalkib in tumori solidi avanzati positivi ALK oltre il NSCLC, con cutoff dei dati al 7 agosto 2025. Tra 34 pazienti valutabili per risposta in 14 tipi di tumore, la risposta obiettiva globale era 44% (15/34), includendo 9/13 naïve agli inibitori TKI ALK e 6/21 precedentemente trattati con TKI. La maggior parte dei pazienti (32/34) ha ricevuto la dose raccomandata di Fase 2 di 150 mg una volta al giorno. Le risposte includonovano risposte di caso durature in corso da ~10–16 mesi e una risposta completa intracranica confermata. La sicurezza è stata descritta come generalmente ben tollerata con riduzioni di dose dell'8,8% e nessuna interruzione dovuta al trattamento al cutoff. L’arruolamento globale in Fase 2 prosegue; i dati principali di Fase 3 per NSCLC sono attesi entro la fine del 2025.
Nuvalent (NASDAQ: NUVL) informó datos preliminares de ALKOVE-1 para neladalkib en tumores sólidos avanzados ALK‑positivos más allá del NSCLC con un punto de corte de datos del 7 de agosto de 2025. Entre 34 pacientes evaluables para respuesta en 14 tipos de tumor, la tasa global de respuesta objetiva fue 44% (15/34), incluyendo 9/13 naïve a TKI ALK y 6/21 pretratados con TKI. La mayoría de los pacientes (32/34) recibió la dosis recomendada de Fase 2 de 150 mg una vez al día. Las respuestas incluyeron respuestas de estudio de caso duraderas de ~10–16 meses y una respuesta completa intracraneal confirmada. La seguridad se describió como generalmente bien tolerada con un 8,8% de reducciones de dosis y ninguna discontinuación relacionada con el tratamiento a la fecha de corte. El reclutamiento global de Fase 2 continúa; se esperan datos principales de NSCLC de la Fase 3 para finales de 2025.
뉴발렌트(NASDAQ: NUVL)은 7aug2025까지의 데이터 컷오프를 가진 알코브-1의 neladalkib에 대한 데이터—NSCLC를 넘어서는 고도 ALK-양성 고형종양에서 발표했습니다. 응답 평가 가능한 34명의 환자에서 14종류의 종양에 대해 전체 객관적 반응률은 44% (15/34)였으며, 그 중 ALK TKI-미경험 9/13, TKI-선치료 6/21 환자가 포함되었습니다. 대부분의 환자(32/34)는 권고된 2상 용량인 매일 150 mg을 받았습니다. 반응은 약 ~10–16개월 지속되는 사례 연구의 반응과 확인된 두경 intracranial 완전 반응 한 건을 포함했습니다. 안전성은 대체로 잘 견디는 것으로 기술되었으며 용량 감소 8.8%, 치료 관련 중단 없음으로 요약됩니다. 글로벌 2상 모집은 계속되며, NSCLC에 대한 2단계의 topline 주요 데이터는 2025년 말로 예상됩니다.
Nuvalent (NASDAQ: NUVL) a publié des données préliminaires ALKOVE-1 pour le neladalkib chez des tumeurs solides avancées ALK‑positives en dehors du NSCLC, avec une coupure de données au 7 août 2025. Parmi 34 patients éligibles à la réponse dans 14 types de tumeurs, le taux global de réponse objective était de 44% (15/34), incluant 9/13 naïfs ALK TKI et 6/21 prétraités par TKI. La plupart des patients (32/34) ont reçu la dose recommandée de la phase 2 de 150 mg une fois par jour. Les réponses comprenaient des réponses de cas durables sur ~10–16 mois et une réponse intracrânienne complète confirmée. La sécurité était décrite comme généralement bien tolérée avec réductions de dose de 8,8% et aucune interruption liée au traitement à la coupure. Le recrutement mondial de la phase 2 se poursuit; les données phares de phase 3 pour le NSCLC sont attendues d’ici fin 2025.
Nuvalent (NASDAQ: NUVL) meldete vorläufige ALKOVE-1-Daten zu Neladalkib in fortgeschrittenen ALK-positiven soliden Tumoren außerhalb des NSCLC mit einem Datenstichtag vom 7. August 2025. Unter 34 responserfassbaren Patienten in 14 Tumortypen betrug die globale objektive Ansprechrate 44% (15/34), einschließlich 9/13 ALK‑TKI‑naïve und 6/21 TKI‑vorbehandelte Patienten. Die meisten Patienten (32/34) erhielten die empfohlene Phase‑2‑Dosis von 150 mg einmal täglich. Zu den Antworten gehörten dauerhafte Einzelbericht‑Antworten über ca. 10–16 Monate und eine bestätigte intracraniale komplette Reaktion. Die Sicherheit wurde allgemein gut verträglich beschrieben mit 8,8% Dosisreduktionen und keine behandlungsbedingten Abbrüche zum Cutoff. Die globale Phase‑2‑Recruitment läuft weiter; topline pivotal NSCLC‑Daten werden bis Ende 2025 erwartet.
نووالينت (بورصة ناسداك: NUVL) أبلغت عن بيانات ALKOVE-1 الأولية لـ neladalkib في الأورام الصلبة المعتمدة على ALK الإيجابية المتقدمة خارج NSCLC، مع نقطة قطع بيانات بتاريخ 7 أغسطس 2025. من بين 34 مريضا قابلا للتقييم للاستجابة عبر 14 نوعا من الأورام، كان معدل الاستجابة الموضوعية الإجمالية 44% (15/34)، بما في ذلك 9/13 من مرضى ALK TKI‑naïve و6/21 تم علاجهم سابقاً بـ TKI. غالبيتهم من المرضى (32/34) تلقوا الجرعة الموصى بها للمرحلة 2 وهي 150 ملغ مرة يومياً. شملت الاستجابات حالات دراسة حالة دائمة لمدة نحو 10–16 شهراً واستجابة intracranial كاملة مؤكدة. وُصفت السلامة بأنها عموماً جيدة التحمل مع خفض الجرعة 8.8% و لا إجراءات إيقاف مرتبطة بالعلاج حتى Cutoff. يستمر التوظيف العالمي للمرحلة 2؛ من المتوقع أن تكون بيانات NSCLC الحاسمة في المرحلة 2 من NSCLC منشورة بنهاية 2025.
Nuvalent (NASDAQ: NUVL) 报告了 neladalkib 在晚期 ALK 阳性实体肿瘤（超越 NSCLC）中的 ALKOVE-1 初步数据，数据截止日为 2025 年 8 月 7 日。在 34 名可评估应答的患者，覆盖 14 种肿瘤类型，总体客观反应率为 44%（15/34），其中 ALK TKI‑naïve 9/13，TKI‑pretreated 6/21。大多数患者（32/34）接受了推荐的二期剂量 150 mg 每日一次。应答包括持续大约 10–16 个月的个案研究应答，以及一例确诊的颅内完全缓解。安全性总体被描述为良好耐受，截止时为 用药减少 8.8%，无治疗相关中止。全球二期募集中继续；预计在 2025 年底公布 NSCLC 的关键二期数据。
- Objective response rate 44% (15/34)
- TKI‑naïve ORR 69% (9/13)
- Most patients (32/34) on 150 mg once daily
- 80% of responders remained on treatment at cutoff
- No discontinuations due to treatment-related adverse events
- Small dataset: 34 response-evaluable patients
- Lower ORR in TKI‑pretreated patients 29% (6/21)
- Preliminary results not yet pivotal or final
Insights
Preliminary Phase 1/2 data show meaningful activity and tolerability of neladalkib across diverse ALK+ non‑NSCLC tumors.
Neladalkib demonstrated an overall objective response rate of
Safety signals appear favourable: low dose‑reduction rate (
Key dependencies and near‑term milestones include maturation of responses, broader cohort enrollment in the global Phase 2, and the planned topline pivotal NSCLC readout by
Encouraging preliminary activity observed across diverse set of advanced ALK-positive solid tumors
Global enrollment ongoing for adult and adolescent patients with advanced ALK-positive solid tumors beyond NSCLC in a Phase 2 cohort of the ALKOVE-1 trial
"Neladalkib was designed with the goal of being a best-in-class ALK-selective inhibitor, and initial clinical safety and efficacy data have been reported in TKI pre-treated ALK-positive NSCLC with topline pivotal data expected by the end of this year. Today, we're excited to share the first report of neladalkib's encouraging preliminary activity beyond NSCLC, which continue to demonstrate its target characteristics of activity against ALK and ALK resistance mutations, brain penetrance, and avoidance of TRK inhibition associated with off-target CNS adverse events," saidChristopher Turner, M.D., Chief Medical Officer of Nuvalent. "These data highlight the potential for an ALK-selective inhibitor to broadly address medical needs for patients with ALK-positive solid tumors, and the importance of widespread genomic testing. We continue to enroll adult and adolescent TKI naïve and TKI pre-treated patients with advanced ALK-positive solid tumors beyond NSCLC in the global Phase 2 portion of our ALKOVE-1 study, and look forward to providing additional updates as these data mature."
Preliminary data are reported for 34 response-evaluable patients enrolled across 14 solid tumor types outside of NSCLC in the Phase 1 and Phase 2 portions of the ALKOVE-1 clinical trial as of a data cutoff date of August 7, 2025. The majority (32/34) of patients received the recommended Phase 2 dose of 150 mg once daily. Patients were ALK TKI-naïve (
Among all patients with advanced ALK-positive solid tumors treated with neladalkib, an objective response rate of
- Treatment ongoing for approximately 12 months with partial response in a TKI-naïve patient with an inflammatory myofibroblastic tumor previously treated with standard of care chemotherapy;
- Treatment ongoing for approximately 16 months with partial response in a TKI and chemotherapy pre-treated patient with peritoneal mesothelioma; and,
- Treatment ongoing for approximately 10 months with confirmed intracranial complete response in a TKI pre-treated patient with adenocarcinoma of unknown origin with baseline brain metastasis and ALK V1180L resistance mutation.
Among these 34 patients, neladalkib was generally well-tolerated with low rates of dose reduction (
Enrollment is ongoing in the global Phase 2 cohort of the ALKOVE-1 trial for adult and adolescent patients with advanced ALK-positive solid tumors other than NSCLC.
The company remains on track to report topline data for patients with TKI pre-treated ALK-positive NSCLC from the ALKOVE-1 trial by the end of 2025. Neladalkib is also being evaluated in ALKAZAR, a global Phase 3 randomized, controlled trial for the treatment of patients with TKI-naïve ALK-positive 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 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 Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Nuvalent's strategy, business plans, and focus; the expected timing of data announcements; the clinical development programs for neladalkib; the potential benefits and effects of Nuvalent's product development candidates; the design and enrollment of the ALKOVE-1 trial; the potential of Nuvalent's pipeline programs, including neladalkib; the implications of data readouts and presentations; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development. The words "may," "might," "will," "could," "would," "should," "plan," "anticipate," "aim," "goal," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" or the negative of these terms and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on these statements or the scientific data presented.
Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: risks that Nuvalent may not fully enroll its clinical trials or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies or clinical trials; the risk that results of earlier clinical trials may not be predictive of the results of later-stage clinical trials; the risk that data from our clinical trials may not be sufficient to support registration and that Nuvalent may be required to conduct one or more additional studies or trials prior to seeking registration of our product candidates; the occurrence of adverse safety events; risks that the FDA may not approve our potential products on the timelines we expect, or at all; risks of unexpected costs, delays, or other unexpected hurdles; risks that Nuvalent may not be able to nominate drug candidates from its discovery programs; the direct or indirect impact of public health emergencies or global geopolitical circumstances on the timing and anticipated timing and results of Nuvalent's clinical trials, strategy, and future operations; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; and risks related to obtaining, maintaining, and protecting Nuvalent's intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Nuvalent's Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, as well as any prior and subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Nuvalent's views only as of today and should not be relied upon as representing its views as of any subsequent date. Nuvalent explicitly disclaims any obligation to update any forward-looking statements.
View original content to download multimedia:https://www.prnewswire.com/news-releases/nuvalent-presents-preliminary-data-for-neladalkib-in-advanced-alk-positive-solid-tumors-beyond-nsclc-at-esmo-2025-302588111.html
SOURCE Nuvalent, Inc.
FAQ
What were neladalkib results reported by Nuvalent (NUVL) at ESMO 2025?
How did neladalkib perform in ALK TKI‑naïve versus pretreated patients in the ALKOVE-1 trial?
What dose of neladalkib was used in most ALKOVE-1 patients (NUVL)?
Were there any serious safety discontinuations for neladalkib in the reported dataset?
Are neladalkib data beyond NSCLC considered durable in ALKOVE-1?
When will Nuvalent (NUVL) report topline ALKOVE-1 pivotal NSCLC data?
