Petosemtamab granted Breakthrough Therapy designation by the U.S. FDA for 1L PD-L1 positive head and neck squamous cell carcinoma
Merus N.V. (Nasdaq: MRUS) has received a second Breakthrough Therapy designation (BTD) from the FDA for petosemtamab in combination with pembrolizumab. This designation is for first-line treatment of adult patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma (r/m HNSCC) with CPS ≥ 1.
The BTD is supported by updated data from an ongoing phase 1/2 trial, which showed a 67% response rate among 24 evaluable patients. This follows the initial BTD and Fast Track designation received in May 2024 and August 2023 for petosemtamab in treating r/m HNSCC patients whose disease progressed after platinum-based chemotherapy and anti-PD-1 antibody treatment.
The BTD status will expedite development and review processes, providing intensive FDA guidance and eligibility for rolling review and priority review. Merus plans to engage with the FDA as they work toward a potential Biologics License Application (BLA) submission.
Merus N.V. (Nasdaq: MRUS) ha ricevuto una seconda designazione di Terapia Innovativa (BTD) dalla FDA per il petosemtamab in combinazione con il pembrolizumab. Questa designazione è per il trattamento di prima linea di pazienti adulti con carcinoma squamoso a cellule del collo e della testa (r/m HNSCC) positivo per PD-L1 con CPS ≥ 1.
La BTD è supportata da dati aggiornati di uno studio clinico di fase 1/2 in corso, che ha mostrato un 67% di tasso di risposta tra 24 pazienti valutabili. Questo segue la prima BTD e la designazione Fast Track ricevute a maggio 2024 e agosto 2023 per il petosemtamab nel trattamento di pazienti con r/m HNSCC la cui malattia è progredita dopo chemioterapia a base di platino e trattamento con anticorpi anti-PD-1.
Lo stato di BTD accelererà i processi di sviluppo e revisione, fornendo una guida intensiva della FDA e l'idoneità per la revisione continua e la revisione prioritaria. Merus prevede di interagire con la FDA mentre lavora verso una potenziale presentazione di domanda di licenza biologica (BLA).
Merus N.V. (Nasdaq: MRUS) ha recibido una segunda designación de Terapia Innovadora (BTD) de la FDA para el petosemtamab en combinación con pembrolizumab. Esta designación es para el tratamiento de primera línea de pacientes adultos con carcinoma de células escamosas de cabeza y cuello (r/m HNSCC) positivo para PD-L1 con CPS ≥ 1.
La BTD está respaldada por datos actualizados de un ensayo clínico en fase 1/2 en curso, que mostró una tasa de respuesta del 67% entre 24 pacientes evaluables. Esto sigue a la primera BTD y la designación Fast Track recibidas en mayo de 2024 y agosto de 2023 para el petosemtamab en el tratamiento de pacientes con r/m HNSCC cuya enfermedad progresó después de la quimioterapia basada en platino y el tratamiento con anticuerpos anti-PD-1.
El estado de BTD acelerará los procesos de desarrollo y revisión, proporcionando orientación intensiva de la FDA y elegibilidad para la revisión continua y la revisión prioritaria. Merus planea interactuar con la FDA mientras trabaja hacia una posible presentación de solicitud de licencia biológica (BLA).
Merus N.V. (Nasdaq: MRUS)는 pembrolizumab과 함께 사용되는 petosemtamab에 대해 FDA로부터 두 번째 혁신 치료제(BTD) 지정을 받았습니다. 이 지시는 PD-L1 양성 재발성 또는 전이성 두경부 편평세포암(r/m HNSCC) 환자의 1차 치료를 위한 것입니다. CPS ≥ 1을 가진 성인 환자에게 적용됩니다.
BTD는 진행 중인 1/2상 시험의 업데이트된 데이터에 의해 지원되며, 24명의 평가 가능한 환자 중 67%의 반응률을 보였습니다. 이는 2024년 5월과 2023년 8월에 재발성 HNSCC 환자를 위한 petosemtamab에 대해 받은 최초의 BTD 및 신속 심사 지정을 따르는 것입니다.
BTD 상태는 개발 및 심사 프로세스를 가속화하며, FDA의 집중적인 안내와 연속 심사 및 우선 심사의 자격을 제공합니다. Merus는 생물학적 제품 허가 신청(BLA) 제출을 위한 작업을 진행하면서 FDA와 협력할 계획입니다.
Merus N.V. (Nasdaq: MRUS) a reçu une deuxième désignation de Thérapie Innovante (BTD) de la FDA pour le petosemtamab en combinaison avec le pembrolizumab. Cette désignation concerne le traitement de première ligne des patients adultes atteints d'un carcinome épidermoïde de la tête et du cou (r/m HNSCC) positif pour PD-L1 avec un CPS ≥ 1.
La BTD est soutenue par des données mises à jour d'un essai clinique de phase 1/2 en cours, qui a montré un taux de réponse de 67% parmi 24 patients évaluables. Cela fait suite à la première BTD et à la désignation Fast Track reçues en mai 2024 et août 2023 pour le petosemtamab dans le traitement des patients atteints de r/m HNSCC dont la maladie a progressé après une chimiothérapie à base de platine et un traitement par anticorps anti-PD-1.
Le statut de BTD accélérera les processus de développement et de révision, fournissant une orientation intensive de la FDA et une éligibilité pour une révision continue et une révision prioritaire. Merus prévoit d'interagir avec la FDA alors qu'elle travaille vers une éventuelle soumission de demande de licence biologique (BLA).
Merus N.V. (Nasdaq: MRUS) hat von der FDA eine zweite Breakthrough-Therapie-Bezeichnung (BTD) für Petosemtamab in Kombination mit Pembrolizumab erhalten. Diese Bezeichnung gilt für die Erstlinientherapie von erwachsenen Patienten mit rezidiviertem oder metastasiertem PD-L1-positivem Plattenepithelkarzinom des Kopfes und Halses (r/m HNSCC) mit CPS ≥ 1.
Die BTD wird durch aktualisierte Daten aus einer laufenden Phase-1/2-Studie unterstützt, die eine 67%ige Ansprechrate bei 24 auswertbaren Patienten zeigte. Dies folgt der ursprünglichen BTD und der Fast-Track-Bezeichnung, die im Mai 2024 und August 2023 für Petosemtamab zur Behandlung von r/m HNSCC-Patienten, deren Erkrankung nach einer platinbasierten Chemotherapie und einer Anti-PD-1-Antikörperbehandlung fortgeschritten ist, erhalten wurden.
Der BTD-Status wird die Entwicklungs- und Überprüfungsprozesse beschleunigen, intensive FDA-Anleitungen bieten und die Berechtigung für die fortlaufende Überprüfung und die prioritäre Überprüfung gewähren. Merus plant, mit der FDA in Kontakt zu treten, während sie auf die mögliche Einreichung eines Biologics License Application (BLA) hinarbeiten.
- Received second Breakthrough Therapy designation from FDA, indicating potential substantial improvement over existing therapies
- Strong efficacy data with 67% response rate in phase 1/2 trial
- Expedited development and review process through BTD status
- Potential for rolling review and priority review from FDA
- Small patient sample size (24 evaluable patients) in clinical trial
- Still in clinical trial phase, pending BLA submission and final approval
Insights
The FDA's second Breakthrough Therapy designation for petosemtamab represents a pivotal development in Merus's oncology program, particularly significant as it targets the lucrative first-line treatment setting. The 67% response rate in PD-L1 positive head and neck cancer is remarkably high compared to current standards, where typical response rates with existing first-line treatments hover around 35-40%.
This regulatory milestone carries several strategic advantages. First, it validates Merus's multispecific antibody platform technology, demonstrating the potential for superior efficacy compared to traditional approaches. Second, securing BTD for both first-line and later-line treatments positions petosemtamab as a potential backbone therapy across the entire HNSCC treatment paradigm, significantly expanding its commercial opportunity.
The accelerated regulatory pathway now available through BTD could compress the timeline to market by 6-12 months, providing Merus with a competitive advantage in the $4-5 billion HNSCC market. The company's plan to pursue a Biologics License Application (BLA) is now strengthened by the FDA's acknowledgment of petosemtamab's potential substantial improvement over existing therapies.
The combination with pembrolizumab is particularly strategic, as it aligns with the growing trend toward immunotherapy combinations while potentially offering superior efficacy. This could position Merus to capture significant market share in both the PD-L1 positive first-line setting and the broader HNSCC market.
This marks the second BTD for petosemtamab in HNSCC
UTRECHT, The Netherlands and CAMBRIDGE, Mass., Feb. 18, 2025 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS), a clinical-stage oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics®, Triclonics® and ADClonics®), for cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to petosemtamab in combination with pembrolizumab for the first-line treatment of adult patients with recurrent or metastatic programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (r/m HNSCC) with combined positive score (CPS) ≥ 1.
This second BTD designation follows the initial receipt of BTD and Fast Track designation for petosemtamab for the treatment of patients with r/m HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-programmed cell death protein 1 (anti-PD-1) antibody announced in May 2024 and August 2023, respectively.
BTD is supported by updated data from the ongoing phase 1/2 open-label, multicenter trial evaluating petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) (NCT03526835). Data for this cohort was initially presented at the American Society of Clinical Oncology® (ASCO®) Annual Meeting 2024, which demonstrated a
“We believe petosemtamab’s second BTD continues to validate its potential to become a new standard of care for patients with r/m HNSCC and underscores our commitment to accelerate development of petosemtamab for these patients,” said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. “Importantly, this designation indicates the interim clinical data we shared with the FDA demonstrates petosemtamab’s potential for substantial improvement over available therapies in the 1L PD-L1+ setting.”
BTD is intended to expedite the development and review of a medicine to treat a serious or life-threatening condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on clinically significant endpoints over available therapies. BTD allows for more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review, and eligibility for rolling review and priority review. With this BTD, Merus plans to engage in these discussions with the FDA in an expedited manner as we move toward our goal of a potential Biologics License Application (BLA) submission.
About LiGeR-HN1
LiGeR-HN1, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab in combination with pembrolizumab, compared to pembrolizumab in 1L PD-L1+ r/m HNSCC patients. The trial is open to adult patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial.
About LiGeR-HN2
LiGeR-HN2, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab compared to investigator’s choice of methotrexate, docetaxel, or cetuximab in 2/3L r/m HNSCC patients. The trial is open to adult patients that have progressed on or after anti-PD-1 therapy and platinum-containing therapy. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial.
About Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by
1 Sung et al. CA Cancer J Clin, 71:209-49, 2021; 2 Johnson, D.E., Burtness, B., Leemans, C.R. et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6(1):92, 2020
About Petosemtamab
Petosemtamab, or MCLA-158, is a Biclonics® low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.
About Merus N.V.
Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, Twitter and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, the potential benefits of BTD for petosemtamab’s development for the first-line treatment of adult patients with recurrent or metastatic programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (R/M HNSCC) with CPS ≥ 1 ; Merus’ belief that petosemtamab’s second BTD continues to validate its potential to become a new standard of care for patients with r/m HNSCC; Merus’ commitment to accelerate development of petosemtamab for these patients; Merus’ belief that this designation indicates the interim clinical data shared with the FDA demonstrates petosemtamab’s potential for substantial improvement over available therapies in the 1L PD-L1+ setting; the potential for BTD to expedite the development and review of a medicine to treat a serious or life-threatening condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on clinically significant endpoints over available therapies; the potential of BTD to allow for more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review, and eligibility for rolling review and priority review; and Merus’ plans to engage in these discussions with the FDA in an expedited manner as we move toward our goal of a potential Biologics License Application (BLA) submission. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended September 30, 2024, filed with the Securities and Exchange Commission, or SEC, on October 31, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Multiclonics®, Biclonics®, Triclonics® and ADClonics® are registered trademarks of Merus N.V.
FAQ
What is the response rate of petosemtamab with pembrolizumab in MRUS's Phase 1/2 trial for HNSCC?
When did MRUS receive its first Breakthrough Therapy designation for petosemtamab?
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