Cutaneous Squamous Cell Carcinoma Pipeline Shows Robust Activity with 45+ Therapies in Development
Key Insights
DelveInsight's 2025 pipeline report reveals 45+ companies developing 45+ therapies for cutaneous squamous cell carcinoma (search), indicating strong industry interest in addressing this aggressive skin cancer (search).
Recent clinical trials include H. Lee Moffitt Cancer Center testing afatinib for advanced cSCC, Regeneron evaluating neoadjuvant cemiplimab, and Daiichi Sankyo assessing ifinatamab deruxtecan across multiple tumor types.
Leading pipeline candidates include HLX07 (Shanghai Henlius Biotech (search)) in Phase II, Opzelura (Incyte Corporation) in Phase II, and RM-1995 (Rakuten Medical (search)) in Phase I trials.
DelveInsight's comprehensive 2025 pipeline analysis reveals a robust therapeutic landscape for cutaneous squamous cell carcinoma (search) (cSCC), with over 45 companies actively developing more than 45 pipeline therapies to address this aggressive form of skin cancer (search). The report highlights significant recent clinical activity and promising emerging treatments across multiple development stages.
Recent Clinical Developments Drive Pipeline Activity
Recent months have witnessed substantial clinical trial activity in the cSCC space. On October 3, 2025, H. Lee Moffitt Cancer Center and Research Institute initiated a study to evaluate whether afatinib can effectively treat participants with advanced cSCC. Concurrently, Regeneron Pharmaceuticals launched a study on September 30, 2025, to assess the efficacy of neoadjuvant cemiplimab, measuring pathologic complete response (pCR) rates through independent central pathology review.
Daiichi Sankyo has also entered the space with a comprehensive study initiated on September 30, 2025, designed to evaluate the efficacy and safety of ifinatamab deruxtecan (I-DXD) across multiple tumor types, including cutaneous melanoma and various carcinomas such as endometrial, head and neck squamous cell, pancreatic ductal adenocarcinoma, and others.
Advanced Pipeline Candidates Show Promise
HLX07: Bio-Better Approach to EGFR Targeting
Shanghai Henlius Biotech (search)'s HLX07, currently in Phase II clinical trials, represents a significant advancement in EGFR (search)-targeted therapy. This bio-better candidate was independently developed using Henlius's advanced antibody engineering platform, re-engineering cetuximab by humanizing its Fab regions and minimizing glycan contents. Preclinical studies demonstrate that HLX07 binds EGFR with similar affinity while showing superior bioactivity compared to cetuximab. The company holds patents for HLX07 across multiple jurisdictions, including China, the United States, the European Union, Australia, and Japan.
Opzelura: First-in-Class Topical JAK Inhibitor
Incyte Corporation's Opzelura, a novel cream formulation of the selective JAK1 (search)/JAK2 (search) inhibitor ruxolitinib, is advancing through Phase II trials for cSCC. The therapy holds the distinction of being the first and only topical JAK inhibitor approved in the United States for topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (search) in non-immunocompromised patients 12 years and older whose disease is inadequately controlled with topical prescription therapies.
RM-1995: Innovative Photo Immunotherapy
Rakuten Medical (search)'s RM-1995, currently in Phase I trials, represents a novel approach using the company's IlluminoxTM platform. This antibody-dye conjugate comprises a monoclonal antibody specific for cell-surface interleukin 2 (IL-2) receptor α-chain (CD25 (search)) and IRDye® 700DX (IR700), a light-activatable dye. The therapy is designed to specifically kill CD25+ regulatory T cells (Tregs) within solid tumors when illuminated with 690nm nonthermal red light.
Preclinical data suggests that RM-1995 photo immunotherapy can specifically deplete intratumoral Tregs, alleviating local Treg-mediated restraint within the tumor microenvironment, rapidly improving the CD8 T cell: Treg ratio, and reinvigorating effector CD8+ T cell responses.
Disease Characteristics Drive Therapeutic Innovation
Cutaneous squamous cell carcinoma (search) represents a common type of keratinocyte cancer derived from cells within the epidermis that produce keratin. As an invasive disease, cSCC involves cancer cells that have grown beyond the epidermis and can sometimes metastasize, potentially proving fatal. More than 90% of cSCC cases are associated with numerous DNA mutations in multiple somatic genes.
Mutations in the p53 tumor suppressor gene, caused by ultraviolet radiation exposure (especially UVB), represent a key driver known as signature 7. Additional signature mutations relate to cigarette smoking, aging, and immune suppression from drugs such as azathioprine. The disease involves mutations in signaling pathways affecting the epidermal growth factor receptor, RAS, Fyn, and p16INK4a signaling.
Diverse Therapeutic Approaches and Administration Routes
The pipeline encompasses diverse therapeutic modalities and administration routes. Companies are developing treatments across multiple delivery methods, including intra-articular, intraocular, intrathecal, intravenous, ophthalmic, oral, parenteral, subcutaneous, topical, and transdermal routes. The molecular diversity spans oligonucleotides, peptides, and small molecules.
Leading companies in the space include Incyte Corporation, Shanghai Henlius Biotech (search), Novartis, Rakuten Medical (search), Morphogenesis, Genentech, Berg Pharma, I-MAB Biopharma, Roche, Genexine, and CureVac. Promising therapies beyond those mentioned include MK-3475A, L19IL2 +L19TNF, cemiplimab, everolimus, and sirolimus.
The therapeutic assessment reveals products categorized as monotherapy, combination therapy, or mono/combination approaches, with clinical stages spanning discovery, preclinical, Phase I, Phase II, and Phase III development. This comprehensive pipeline activity suggests significant industry commitment to addressing the unmet medical needs in cutaneous squamous cell carcinoma (search) treatment.