On December 13, 2024, the FDA approved cosibelimab-ipdl, a PD-L1 blocking antibody, for adults with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation.
Cutaneous Squamous Cell Carcinoma
Cutaneous squamous-cell carcinoma (cSCC) is a common form of skin cancer that originates in the squamous cells of the skin. It typically appears as a firm, scaly bump or an ulcerated lesion and most often develops on areas exposed to the sun, such as the face, ears, neck, and hands. cSCC is more likely to spread to other parts of the body compared to basal-cell carcinoma. The primary risk factor for cSCC is prolonged ultraviolet (UV) radiation exposure, including from sunlight and tanning beds, with other contributing factors being fair skin, chronic wounds, smoking, and a weakened immune system.
The clinical presentation of cSCC is highly variable, with tumors often starting as a small, slow-growing nodule that may ulcerate or bleed intermittently. Lesions may appear as red, scaly plaques or hard papules with small blood vessels. cSCC is frequently associated with actinic keratosis, a precancerous skin condition caused by sun damage. In some cases, it may develop from existing scars or actinic keratoses. Although it typically grows slowly, there is a risk of metastasis, particularly for larger, deeper, or poorly differentiated tumors, or those located in high-risk areas like the lips or ears.
Treatment for cSCC usually involves surgical removal of the tumor, with Mohs surgery used for more complex cases. In advanced stages or when metastasis occurs, radiation therapy, chemotherapy, or biologic treatments may be necessary. Prevention is primarily focused on reducing sun exposure, using sunscreen, and avoiding tanning beds. Regular skin checks are essential for early detection. When caught early and treated appropriately, the prognosis for cSCC is generally favorable, but if the cancer spreads, survival rates can be significantly lower.
Efficacy and Safety of Cosibelimab-ipdl
The efficacy of cosibelimab-ipdl was evaluated in Study titled “Efficacy and safety of cosibelimab, an anti–PD-L1 antibody, in patients with metastatic cutaneous squamous cell carcinoma.” published on Journal of Clinical Oncology, a multicenter, multicohort, open-label trial involving 109 patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced cutaneous squamous cell carcinoma (laCSCC) who were not candidates for curative surgery or radiation. Key exclusion criteria included active or suspected autoimmune diseases, recent allogeneic transplant, prior treatment with anti-PD-1/PD-L1 blocking antibodies or other immune checkpoint inhibitors, uncontrolled cardiovascular disease, ECOG performance status ≥2, and infection with HIV, hepatitis B, or hepatitis C.
Authors: Philip R. Clingan, Daniel Brungs, Susan Arnold, Jermaine Coward, Samuel J. Fourie, Dean Laurence Harris, Andrii Kurochkin, Rahul Ladwa, Niel Malan, Andrew Michael Mant, Margie McGrath, Vinay Sharma, Hong Shue, Andrea Tazbirkova, James Oliviero, and Jayesh Desai
The primary efficacy endpoints were objective response rate (ORR) and duration of response (DOR), as assessed by an independent central review committee (IRC) using RECIST version 1.1. For patients with laCSCC, where externally visible target lesions were not assessable by imaging, ORR was determined by IRC assessments of digital photography (WHO criteria). The ORR was 47% (95% CI: 36-59) for patients with mCSCC (n=78) and 48% (95% CI: 30-67) for those with laCSCC (n=31). The median DOR was not reached in mCSCC patients (range: 1.4+, 34.1+ months) and was 17.7 months (range: 3.7+, 17.7 months) in laCSCC patients.
Adverse Reactions
The most common adverse reactions (≥10%) reported with cosibelimab-ipdl include fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritis, edema, localized infection, and urinary tract infection. These side effects were observed in patients receiving treatment and are important considerations for monitoring and managing patient health during therapy.
The recommended dose of cosibelimab-ipdl is 1,200 mg, administered as an intravenous infusion over a period of 60 minutes, once every 3 weeks. Treatment should continue until either disease progression occurs or unacceptable toxicity is observed. This dosing schedule aims to balance therapeutic efficacy while minimizing risks associated with prolonged treatment.
This review of cosibelimab-ipdl’s safety and efficacy utilized the Assessment Aid, which is a voluntary submission from the applicant. This aid was designed to facilitate the FDA’s thorough review of the drug, ensuring that all relevant data and safety information were considered in making the approval decision.
About the Author of the Study – Philip Clingan
Professor Philip Clingan is a prominent medical professional and educator, currently serving as a Professor at the Graduate School of Medicine at the University of Wollongong. He holds the position of Director of the Department of Medical Oncology at the Illawarra Shoalhaven Local Health District, where he plays a key role in the advancement of oncology care and research. Additionally, he serves as the Medical Director of the Southern Medical Day Care Centre, contributing to patient care in the region.
Professor Clingan is deeply involved in medical education, particularly in the training of medical students at the University of Wollongong. He is also closely associated with the Illawarra Health and Medical Research Centre, where he collaborates on various research initiatives to advance knowledge in the medical field, particularly in oncology.
He holds hospital affiliations with several institutions, including Wollongong Hospital, Shoalhaven Hospital, Figtree Private Hospital, and St George Hospital NSW, where he contributes to patient care, particularly in medical oncology. He is also affiliated with key clinics such as the Southern Medical Day Care Centre and the Illawarra Cancer Care Centre, which are central to cancer treatment and care in the region.
Professor Clingan is an active member of several professional organizations, including the Royal Australasian College of Physicians (RACP) and the Medical Oncology Group of Australia (MOGA). These affiliations highlight his commitment to the ongoing development of medical oncology in Australia. Through his academic and clinical work, Professor Clingan has made significant contributions to the medical field, particularly in oncology.