petosemtamab (MCLA-158)

Emerging agents such as ficerafusp alfa, petosemtamab, and amivantamab have demonstrated promising early clinical activity, particularly in biomarker-enriched or post-immunotherapy settings. In HPV-positive disease, therapeutic vaccines targeting E6/E7 oncoproteins have shown encouraging immunogenicity and preliminary antitumor activity, especially when combined with PD-1 blockade. Overall, the immunotherapeutic landscape of OPSCC is evolving toward a biomarker-driven framework integrating viral status, immune contexture and pathway activation to enable more precise and personalized treatment strategies.

P1/2, N=90, Recruiting, Merus B.V. | N=45 --> 90

P1/2, N=90, Recruiting, Merus B.V. | Not yet recruiting --> Recruiting

P3, N=700, Recruiting, Merus B.V. | N=500 --> 700

P1/2, N=45, Not yet recruiting, Merus N.V.

P2, N=180, Recruiting, Merus B.V. | Initiation date: Dec 2025 --> Mar 2025

Recent advances highlight a rapid surge in positive immunotherapy trials across different head and neck cancer entities, with clinical benefit observed both when immune checkpoint inhibitors are moved earlier in the disease course and when they are combined with agents targeting resistance mechanisms or enabling more precise drug delivery to tumors.

Cetuximab, a chimeric IgG1 monoclonal antibody anti-EGFR, is the only EGFR-targeted agent approved for HNSCC and has shown efficacy in both locally advanced (in platinum-unfit patients) and recurrent/metastatic (R/M) settings...Irreversible pan-HER tyrosine kinase inhibitors (e.g., afatinib, dacomitinib), dual-target bispecific antibodies such as duligotuzumab (EGFR/HER3), petosemtamab (EGFR/LGR5) or ficerafusp alfa (EGFR/TGF-β) have led to promising preclinical and early-phase clinical activity...While EGFR remains a valid therapeutic target, future efforts must focus on biomarker-driven patient selection and combination strategies to enhance efficacy and durability of response. Ongoing trials will further define the role of emerging anti-EGFR agents and their integration into HNSCC treatment algorithms.

P2, N=180, Recruiting, Merus N.V.

LiGeR-HN2 (NCT06496178) evaluates petosemtamab versus investigator's choice of monotherapy (cetuximab, methotrexate, or docetaxel) in patients with previously treated r/m HNSCC. Primary endpoints in both trials are objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review, and overall survival. Both trials are recruiting at the time of publication.Clinical Trial Registration: NCT06525220 and NCT06496178 (ClinicalTrials.gov).

The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC.

P3, N=500, Recruiting, Merus N.V. | Not yet recruiting --> Recruiting