On September 28, 2018, cemiplimab-rwlc (Libtayo) was approved for the treatment of patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation.¹

Supporting Efficacy Data

Approval was based on the finding of durable objective responses in a total of 108 patients with advanced cutaneous squamous cell carcinoma who received cemiplimab-rwlc at 3 mg/kg intravenously every 2 weeks. Patients were enrolled in either study R2810-ONC-1423 (n = 26), an open-label, multicenter, dose-finding trial with expansion cohorts in patients with various advanced solid tumors, or study R2810-ONC-1540 (n = 82), an open-label, multicenter, nonrandomized, multicohort trial in patients with metastatic or locally advanced cutaneous squamous cell carcinoma, regardless of prior treatment, for whom surgery or radiation was not recommended.^1–3

Treatment was administered for up to 48 weeks in study 1423 and up to 96 weeks in study 1540. Objective response rates were assessed by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) for patients with metastatic cutaneous squamous cell carcinoma. A composite response assessment incorporating clinical response criteria using digital photography and RECIST 1.1 was used for patients with locally advanced cutaneous squamous cell carcinoma.

Among the 108 patients, 75 had metastatic cutaneous squamous cell carcinoma and 33 had locally advanced cutaneous squamous cell carcinoma. Among patients with metastatic cutaneous squamous cell carcinoma, 69% had distant metastases and 31% had nodal metastases alone.

Among all 108 patients, the objective response rate was 47%, including complete response in 4%. Objective response rates were 47% (complete response in 5%) among the 75 patients with metastatic disease and 49% (all partial responses) among the 33 with locally advanced disease. The median duration of response was not reached, with ranges of 1.0 to 15.2+ months in all patients, 2.8 to 15.2+ months in those with metastatic disease, and 1 to 12.9+ months in those with locally advanced disease. Overall, 61% of responders had a response for at least 6 months, including 60% of those with metastatic disease and 63% of those with locally advanced disease.

How It Works

Cemiplimab-rwlc is a recombinant human immunoglobulin G4 (IgG4) programmed cell death protein 1 (PD-1)-blocking monoclonal antibody that binds to PD-1 and blocks its interaction with programmed cell death ligand 1 (PD-L1) and PD-L2, releasing PD-1 pathway–mediated inhibition of the immune response, including antitumor immune response. In syngeneic mouse tumor models, blocking of PD-1 activity resulted in decreased tumor growth.

Binding of the PD-1 ligands PD-L1 and PD-L2 to PD-1 receptors found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.

How It Is Used

The recommended dosage of cemiplimab-rwlc is 350 mg via intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Product labeling provides instructions for management of immune-related and other toxicities associated with treatment. No dose reduction of cemiplimab-rwlc is recommended.

Treatment should be withheld for grade 2 pneumonitis, grade 2 or 3 colitis, hepatitis with aspartate transaminase (AST) or alanine transaminase (ALT) increases to more than 3 and up to 10 times the upper limit of normal (ULN) or total bilirubin increases up to 3 times ULN, and other grade 3 immune-mediated adverse reactions involving a major organ. The drug should also be withheld if clinically necessary for grade 2 to 4 endocrinopathies. After withholding cemiplimab-rwlc and treating the patient with corticosteroids, therapy can be resumed with resolution of toxicity to grade 0 or 1 after corticosteroid taper.

Treatment should be permanently discontinued for grade 3 or 4 pneumonitis, grade 4 colitis, hepatitis with AST or ALT increases to more than 10 times ULN or total bilirubin increases to more than 3 times ULN, and other grade 4 immune-mediated adverse reactions involving a major organ. Infusion should be interrupted or slowed for grade 1 or 2 infusion-related reactions, and treatment should be discontinued for grade 3 or 4 reactions.

Safety Profile

Safety data are from 163 patients with advanced cutaneous squamous cell carcinoma in study 1423 and study 1540, of whom 162 received 3 mg/kg every 2 weeks (n = 139) or 350 mg every 3 weeks (n = 23). The most common adverse events of any grade (≥ 20% of patients) were fatigue (29%), rash (25%), and diarrhea (22%). The most common grade 3 or 4 adverse events occurring in ≥ 2% of patients were cellulitis, sepsis, hypertension, pneumonia, musculoskeletal pain, skin infection, urinary tract infection, and fatigue. The most common grade 3 or 4 laboratory abnormalities were lymphopenia (7%), hypophosphatemia (4%), and increased AST (3%).

Serious adverse events occurred in 28% of patients, with those occurring in ≥ 2% of patients being cellulitis, sepsis, pneumonia, pneumonitis, and urinary tract infection. Treatment was permanently discontinued due to adverse events in 5% of patients, with causes consisting of pneumonitis, autoimmune myocarditis, hepatitis, aseptic meningitis, complex regional pain syndrome, cough, and muscular weakness.

Cemiplimab-rwlc has warnings/precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, and embryofetal toxicity. Patients should be advised not to breastfeed during treatment with cemiplimab-rwlc.

Immune-mediated adverse reactions can occur in any organ system or tissue and include immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic adverse reactions, nephritis, and renal dysfunction. Patients should be monitored for symptoms and signs of immune-mediated adverse reactions. Clinical chemistries, including liver and thyroid function tests, should be monitored at baseline and periodically during treatment. ■

REFERENCES

1. U.S. Food and Drug Administration: FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm622251.htm. Accessed October 3, 2018.

2. Libtayo (cemiplimab-rwlc) injection prescribing information, Regeneron Pharmaceuticals, Inc/Sanofi-Aventis US LLC, September 2018. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2018/761097s000lbl.pdf. Accessed October 3, 2018.

3. Migden MR, Rischin D, Schmults CD, et al: PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 379:341-351, 2018.