Nuvalent Announces First Patient Dosed in HEROEX-1 Phase 1a/1b Clinical Trial of NVL-330, its Novel HER2-selective Inhibitor
Nuvalent (Nasdaq: NUVL) has announced the initiation of HEROEX-1, a Phase 1a/1b clinical trial evaluating its novel HER2-selective inhibitor, NVL-330, for pre-treated patients with HER2-altered non-small cell lung cancer (NSCLC). The trial aims to assess the safety, tolerability, and preliminary anti-tumor activity of NVL-330, as well as determine the recommended Phase 2 dose and characterize its pharmacokinetic profile.
NVL-330 has shown potential in preclinical studies to maintain activity against HER2 exon 20 mutations, be selective for HER2 versus wild-type EGFR, and demonstrate brain penetrance. These characteristics address key needs in HER2-mutant NSCLC treatment, for which there are currently no approved tyrosine kinase inhibitors (TKIs).
This marks Nuvalent's third program to enter clinical development in under three years, highlighting the company's commitment to rapid progress in developing targeted cancer therapies.
Nuvalent (Nasdaq: NUVL) ha annunciato l'inizio di HEROEX-1, uno studio clinico di Fase 1a/1b che valuta il suo nuovo inibitore selettivo dell'HER2, NVL-330, per pazienti pretrattati con cancro polmonare non a piccole cellule (NSCLC) alterato da HER2. Lo studio punta a valutare la sicurezza, la tollerabilità e l'attività antitumorale preliminare di NVL-330, così come a determinare la dose raccomandata per la Fase 2 e a caratterizzarne il profilo farmacocinetico.
NVL-330 ha mostrato potenziale negli studi preclinici per mantenere l'attività contro le mutazioni dell'esone 20 di HER2, essere selettivo per HER2 rispetto all'EGFR wild-type e dimostrare capacità di penetrazione nel cervello. Queste caratteristiche soddisfano esigenze chiave nel trattamento del NSCLC mutante HER2, per il quale attualmente non esistono inibitori della tirosina chinasi (TKI) approvati.
Questo segna il terzo programma di Nuvalent a entrare nello sviluppo clinico in meno di tre anni, evidenziando l'impegno dell'azienda per un rapido progresso nello sviluppo di terapie oncologiche mirate.
Nuvalent (Nasdaq: NUVL) ha anunciado el inicio de HEROEX-1, un ensayo clínico de Fase 1a/1b que evalúa su novedoso inhibidor selectivo de HER2, NVL-330, para pacientes pretratados con cáncer de pulmón no de pequeñas células (NSCLC) con alteraciones en HER2. El ensayo tiene como objetivo evaluar la seguridad, la tolerabilidad y la actividad anti-tumoral preliminar de NVL-330, así como determinar la dosis recomendada para la Fase 2 y caracterizar su perfil farmacocinético.
NVL-330 ha mostrado un potencial en estudios preclínicos para mantener actividad contra mutaciones del exón 20 de HER2, ser selectivo para HER2 frente al EGFR tipo salvaje y demostrar penetración en el cerebro. Estas características abordan necesidades clave en el tratamiento de NSCLC mutante HER2, para el cual actualmente no hay inhibidores de tirosina quinasa (TKI) aprobados.
Este es el tercer programa de Nuvalent en entrar en desarrollo clínico en menos de tres años, destacando el compromiso de la empresa con un progreso rápido en el desarrollo de terapias contra el cáncer dirigidas.
Nuvalent (Nasdaq: NUVL)은 HER2 변이 비소세포 폐암(NSCLC)으로 처치받은 환자를 위한 혁신적인 HER2 선택적 억제제 NVL-330에 대한 1a/1b 단계의 임상 시험인 HEROEX-1의 시작을 발표했습니다. 이 시험은 NVL-330의 안전성, 내약성 및 초기 항종양 활성을 평가하고, 2단계 권장 용량을 결정하며 약리학적 프로필을 특성화하는 것을 목표로 합니다.
NVL-330은 전임상 연구에서 HER2 엑손 20 변이에 대한 활성을 유지하고, 야생형 EGFR에 비해 HER2에 선택적이며, 뇌 침투 가능성을 보여준 잠재력을 가지고 있습니다. 이러한 특성은 현재 승인된 티로신 키나제 억제제(TKI)가 없는 HER2 변이 NSCLC 치료에서 중요한 요구를 충족시킵니다.
이는 Nuvalent가 3년 이내에 임상 개발에 진입한 세 번째 프로그램으로, 목표 지향적인 암 치료제 개발에 대한 회사의 의지를 강조합니다.
Nuvalent (Nasdaq: NUVL) a annoncé le lancement de HEROEX-1, un essai clinique de Phase 1a/1b qui évalue son nouvel inhibiteur sélectif de HER2, NVL-330, pour des patients prétraités atteints de cancer du poumon non à petites cellules (NSCLC) avec des altérations de HER2. L'essai vise à évaluer la sécurité, la tolérance et l'activité antitumorale préliminaire de NVL-330, ainsi qu'à déterminer la dose recommandée pour la Phase 2 et à caractériser son profil pharmacocinétique.
NVL-330 a montré un potentiel lors d'études précliniques pour maintenir l'activité contre les mutations de l'exon 20 de HER2, être sélectif pour HER2 par rapport à l'EGFR sauvage et démontrer une pénétration cérébrale. Ces caractéristiques répondent à des besoins clés dans le traitement du NSCLC mutant HER2, pour lequel il n'existe actuellement aucun inhibiteur de la tyrosine kinase (TKI) approuvé.
C'est le troisième programme de Nuvalent à entrer en développement clinique en moins de trois ans, soulignant l'engagement de l'entreprise envers des progrès rapides dans le développement de thérapies ciblées contre le cancer.
Nuvalent (Nasdaq: NUVL) hat den Start von HEROEX-1 angekündigt, einer Phase 1a/1b-Studie, die seinen neuartigen HER2-selektiven Inhibitor NVL-330 bei vorbehandelten Patienten mit HER2-verändertem nicht-kleinzelligem Lungenkrebs (NSCLC) bewertet. Die Studie zielt darauf ab, die Sicherheit, Verträglichkeit und vorläufige antitumorale Aktivität von NVL-330 zu bewerten und die empfohlene Dosis für Phase 2 zu bestimmen und das pharmakokinetische Profil zu charakterisieren.
NVL-330 hat in präklinischen Studien Potenzial gezeigt, die Aktivität gegen HER2 Exon 20 Mutationen aufrechtzuerhalten, selektiv für HER2 gegenüber wildtypischem EGFR zu sein und eine Hirndurchdringung zu demonstrieren. Diese Eigenschaften sprechen wichtige Bedürfnisse in der Behandlung von HER2-mutiertem NSCLC an, für das derzeit keine zugelassenen Tyrosinkinase-Inhibitoren (TKIs) existieren.
Dies ist das dritte Programm von Nuvalent, das in weniger als drei Jahren in die klinische Entwicklung eintritt, was das Engagement des Unternehmens für schnellen Fortschritt bei der Entwicklung gezielter Krebstherapien hervorhebt.
- Initiation of Phase 1a/1b clinical trial for NVL-330 in HER2-altered NSCLC
- NVL-330 shows potential for differentiated profile in preclinical studies
- Third program from Nuvalent's pipeline to enter clinical development in under three years
- None.
The initiation of the HEROEX-1 clinical trial marks an important milestone in the development of novel targeted therapies for HER2-altered non-small cell lung cancer (NSCLC). HER2 mutations, particularly exon 20 mutations, present a challenging subset of oncogenic drivers in NSCLC with limited treatment options. Although HER2-targeted therapies exist, they often lack effectiveness against these specific mutations and come with significant side effects. NVL-330's unique profile—being selective for HER2 over wild-type EGFR to reduce gastrointestinal and skin toxicities and having the potential to penetrate the brain—addresses critical gaps in current treatment strategies.
From a clinical perspective, the trial’s focus on safety, tolerability and preliminary anti-tumor activity is crucial. If NVL-330 can demonstrate efficacy with a manageable safety profile, it could significantly improve outcomes for patients with HER2-altered NSCLC, who currently have limited therapeutic options. This makes NVL-330 a candidate to watch closely in the oncology space.
The Phase 1a/1b trial for NVL-330 represents a critical step in evaluating a promising candidate within the competitive landscape of targeted cancer therapies. The clear objectives of determining the recommended Phase 2 dose, characterizing the pharmacokinetic profile and assessing preliminary anti-tumor activity will provide valuable data for subsequent development stages. NVL-330's differentiation through its selectivity and brain penetration capabilities could position it uniquely in a market where effective HER2 inhibitors for exon 20 mutations in NSCLC are lacking.
Nuvalent's rapid advancement from preclinical to clinical stages for multiple programs within three years underscores its robust research and development capabilities. Investors should monitor the trial's progress closely, as positive results could not only propel NVL-330 into later-stage trials but also enhance Nuvalent's market position and valuation.
Nuvalent's announcement of dosing the first patient in their HEROEX-1 trial is a significant development for the company and the broader market. This milestone reflects the company's operational efficiency and commitment to advancing its pipeline swiftly. The fact that this is the third program to enter clinical development within three years illustrates a strong and aggressive approach to pipeline expansion, which is generally favorable for the company's long-term growth prospects.
For investors, this trial initiation could signal potential upside if the drug proves to be safe and effective. Positive early-phase data often lead to increased investor confidence and stock price appreciation. However, investors should also remain mindful of the inherent risks in clinical trials, including potential setbacks in drug development. Overall, the news is a positive indicator of Nuvalent's strategic execution and potential future success.
"HER2 alterations are an important category of oncogenic drivers within NSCLC that includes both HER2 amplification and HER2 mutations, the majority of which are exon 20 mutations. While HER2- targeted therapies have been developed, there are currently no approved TKIs for the HER2-mutant NSCLC patient population," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "At the outset of our program, physician-scientists outlined the need for a HER2 therapy that maintained activity against HER2 exon 20 mutations, was selective for HER2 versus wild-type EGFR to limit gastrointestinal and skin toxicities associated with EGFR inhibition, and was brain penetrant to address and limit brain metastases. NVL-330's preclinical profile has demonstrated the potential to be differentiated through combining these desired characteristics, and supports its initial clinical investigation in our HEROEX-1 trial for patients with HER2-altered NSCLC."
HEROEX-1 is a Phase 1a/1b, multicenter, open-label, dose-escalation and expansion trial evaluating NVL-330 in pre-treated patients with advanced HER2-altered NSCLC, including those with HER2 exon 20 mutations. The trial will evaluate the overall safety and tolerability of NVL-330. Additional objectives include determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and preliminary evaluation of anti-tumor activity.
"The initiation of this trial represents a significant milestone for Nuvalent, marking the third program from our novel pipeline to enter clinical development in under three years," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "This rapid execution serves as a testament to our team's dedication to rapid progress and growth across our pipeline, and our unwavering commitment to our goal of bringing precisely targeted therapies to patients with cancer."
About NVL-330
NVL-330 is a novel brain-penetrant HER2-selective tyrosine kinase inhibitor designed to address the combined medical need of treating HER2-altered tumors, including those with HER2 exon 20 insertion mutations, avoiding treatment related adverse events due to off-target inhibition of wild-type EGFR, and treating brain metastases. NVL-330 is currently being investigated in the HEROEX-1 Phase 1a/1b clinical trial for pre-treated patients with advanced HER2-altered 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 clinical development program for NVL-330; the potential clinical effect of NVL-330; the design of the HEROEX-1 trial; the potential of Nuvalent's pipeline programs, including NVL-330; 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," "expect," "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: 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 quarterly period ended March 31, 2024, 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.
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SOURCE Nuvalent, Inc.
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