On February 18, 2025 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, reported 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 (Press release, Merus, FEB 18, 2025, View Source [SID1234650347]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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) (Free ASCO Whitepaper) Annual Meeting 2024, which demonstrated a 67% response rate among 24 evaluable patients. The oral presentation was detailed in our press release, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024). In the BTD application, Merus provided updated interim clinical data on efficacy, durability and safety of the cohort of petosemtamab with pembrolizumab in 1L PD-L1+ r/m HNSCC.
"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 30% to more than 1 million new cases annually by 2030.2 HNSCC is a serious and life-threatening disease with poor prognosis despite currently available standard of care therapies.
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.