Journal Article

Nivolumab for unresectable cutaneous epithelial malignancies: an open-label, single-arm, multi-centre, phase II trial (NMSC-PD1)

Nakamura, Yoshio, Fusumae, Takayuki, Fujimura, Taku, Takemura, Ryo, Otsuka, Atsushi, Saito, Yasuko, Hirai, Ikuko, Amagai, Masayuki, Mori, Shoichiro, Ogawa-Momohara, Mariko, Sato, Yasunori, Kurimoto, Mana, Yamazaki, Naoya, Kabashima, Kenji, Tanese, Keiji, Namikawa, Kenjiro, Takenouchi, Tatsuya, Funakoshi, Takeru, Yamamoto, Yuki, Uchi, Hiroshi

2026

Overview

Background Data in East Asian patients and in other epithelial skin cancers, including extramammary Paget’s disease (EMPD) and adnexal carcinomas, are scarce. Therefore, we conducted a phase II trial of nivolumab in Japanese patients with advanced non-melanoma skin cancers (NMSCs). Patients and methods This multicentre, open-label, single-arm phase II study enrolled adults (≥ 20 years) with histologically confirmed unresectable or recurrent epithelial cutaneous malignancies, Eastern Cooperative Oncology Group performance status 0–1, and at least one measurable lesion (RECIST v1.1). Nivolumab 480 mg was administered intravenously every 4 weeks for up to 26 cycles. The primary endpoint was overall response rate (ORR), assessed by blinded independent central review (BICR; RECIST v1.1). Secondary endpoints included progression-free survival, overall survival, and safety. Results Thirty-one patients were enrolled (20 cSCC, 4 EMPD, 2 BCC, 5 other NMSCs); median age was 73 years (range 58–86), and 71% were male. ORR by BICR was 22.6% (7/31), and the disease control rate was 54.8% (17/31). Responses were durable, with a median duration of 21.3 months. In the cSCC cohort, median tumour mutational burden (TMB) was 9.0 mut/Mb, lower than in Western series; among three patients with TMB ≥ 30 mut/Mb, two achieved objective responses. Common adverse events included pyrexia, hypothyroidism, adrenal insufficiency, and pruritus. Conclusions Nivolumab showed durable antitumour activity with manageable toxicity in Japanese patients with advanced NMSCs, including rare non-cSCC. The lower ORR compared with Western trials may reflect intrinsic biological differences and support biomarker-driven, region-specific immunotherapy. Clinical trial registration jRCT2031190048; registered 2 July 2019.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Aged, 80 and over / Antibodies / Antineoplastic Agents, Immunological - administration & dosage / Antineoplastic Agents, Immunological - adverse effects / Antineoplastic Agents, Immunological - therapeutic use / Autoimmune diseases / Biomedical and Life Sciences / Biomedicine / Birth control / Breastfeeding & lactation / Cancer Research / Cancer therapies / Clinical trials / Consent / Creatinine / Disease / Disease control / Drug therapy / Epidemiology / Epithelial cells / Epithelial skin malignancy / Female / Fever / Health aspects / Health Promotion and Disease Prevention / Humans / Hypothyroidism / Immune Checkpoint Inhibitors - administration & dosage / Immune Checkpoint Inhibitors - adverse effects / Immune Checkpoint Inhibitors - therapeutic use / Immunotherapy / Male / Malignancy / Medical prognosis / Medicine/Public Health / Melanoma / Metastasis / Middle Aged / Nivolumab / Nivolumab - administration & dosage / Nivolumab - adverse effects / Nivolumab - therapeutic use / Non-melanoma skin cancer / Non-Melanoma Skin Neoplasms - drug therapy / Oncology / PD-1 protein / Pharmacology, Experimental / Physiological aspects / Programmed death-1 / Pruritus / Radiation therapy / Regulatory approval / Response rates / Skin cancer / Skin Neoplasms - drug therapy / Skin Neoplasms - mortality / Skin Neoplasms - pathology / Squamous cell carcinoma / Surgical Oncology / Survival / Toxicity / Treatment Outcome / Tumors