On February 9, 2021, cemiplimab-rwlc was granted regular approval for the treatment of patients with locally advanced basal cell carcinoma (BCC) who were previously treated with a Hedgehog pathway inhibitor or for whom this type of therapy is not appropriate and granted accelerated approval for treatment of patients with metastatic BCC who were previously treated with a hedgehog pathway inhibitor or for whom such an agent is not appropriate.^1,2

Supporting Efficacy Data

Approval was supported by findings from the ongoing multicenter Study 1620 (ClinicalTrials.gov identifier NCT03132636).² The efficacy population for the trial consisted of 112 patients with advanced BCC, including 84 with locally advanced BCC and 28 with metastatic BCC, who had disease progression on hedgehog pathway inhibitor therapy, had not had an objective response after 9 months on such therapy, or were intolerant of prior treatment with these agents. Patients with locally advanced BCC could not be candidates for curative surgery or curative radiotherapy. All patients received cemiplimab at 350 mg every 3 weeks for up to 93 weeks until disease progression, unacceptable toxicity, or completion of planned treatment.

Among patients with locally advanced BCC, the median age was 70 years (range = 42–89 years), 67% were male, and 68% were White. All had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (61%) or 1, 83% had undergone at least one prior cancer-related surgery, and 50% had received prior radiotherapy. Among patients with metastatic BCC, median age was 65.5 years (range = 38–90 years), 82% were male, and 79% were White. All had an ECOG performance status of 0 (57%) or 1, 82% had undergone at least one prior cancer-related surgery, and 61% had received prior radiotherapy. Overall, 32% had distant metastases alone, 14% had nodal disease alone, and 54% had both distant and nodal disease.

The main efficacy outcome measures were confirmed objective response rate and duration of response on independent central review. For patients without externally visible target lesions (metastatic BCC), confirmed objective response was assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). A composite response assessment incorporating clinical response criteria using digital medical photography together with RECIST v1.1 was used for patients with externally visible target lesions (locally advanced and metastatic BCCs).

Among the 84 patients with locally advanced BCC, objective responses were observed in 24 (29%, 95% confidence interval [CI] = 19%–40%), with a complete response in 5 (6%). Median duration of response was not reached (range = 2.1 to 21.4+ months), with 79% of responders maintaining response for at least 6 months. Among the 28 patients with metastatic BCC, objective responses (all partial responses) were observed in 6 (21%, 95% CI = 8%–41%). Median duration of response was not reached (range = 9 to 23.0+ months), with 100% of responders maintaining a response for at least 6 months.

How It Works

Cemiplimab is a recombinant human immunoglobulin G4 PD-1–blocking monoclonal antibody that binds to PD-L1 and blocks its interaction with 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 is 350 mg via intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

No dose reduction is recommended. In general, treatment should be withheld for severe (grade 3) immune-mediated adverse reactions and permanently discontinued for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce the corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Infusion should be interrupted or slowed for grade 1 or 2 infusion-related reactions, and treatment should be permanently discontinued for grade 3 or 4 reactions. Prescribing information provides instructions on management of immune-mediated adverse events, including pneumonitis, colitis, hepatitis with no tumor involvement of the liver, hepatitis with tumor involvement of the liver, endo­crinopathies, nephritis with renal dysfunction, exfoliative dermatologic conditions, myocarditis, and neurologic toxicities.

Safety Profile

Safety data are from a total of 132 patients with advanced BCC (48 with metastatic BCC, 84 with locally advanced BCC) who received cemiplimab at 350 mg every 3 weeks in Study 1620. The median duration of exposure was 42 weeks.

The most common adverse events of any grade were fatigue (49%), musculoskeletal pain (33%), diarrhea (25%), rash (22%), pruritus (20%), and upper respiratory tract infection (15%). The most common grade 3 or 4 adverse events included hypertension (4.5%), fatigue (3.8%), and urinary tract infection (2.3%). The most common grade 3 or 4 laboratory abnormalities that worsened from baseline were hyponatremia (3.4%), prolonged activated partial thromboplastin time (2.3%), and decreased lymphocytes (2.3%).

Serious adverse events occurred in 32% of patients, with those occurring in more than two patients (1.5%) being urinary tract infection, colitis, acute kidney injury, adrenal insufficiency, anemia, infected neoplasm, and somnolence. 

Cemiplimab has warnings/precautions for immune-mediated adverse reactions, including severe and fatal reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. 

REFERENCES

1. U.S. Food and Drug Administration: FDA approves cemiplimab-rwlc for locally advanced and metastatic basal cell carcinoma. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-locally-advanced-and-metastatic-basal-cell-carcinoma. Accessed March 2, 2021.

2. Libtayo (cemiplimab-rwlc) injection, for intravenous use, prescribing information, Regeneron Pharmaceuticals, Inc/sanofi-aventis U.S. LLC, February 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s008lbl.pdf. Accessed March 2, 2021.