Study Confirms Safety and Effectiveness of Cemiplimab in Squamous Cell Carcinoma

Cemiplimab (Libtayo) is an active treatment option for locally advanced cutaneous squamous cell carcinoma and has an acceptable safety profile, according to the results of an international phase II open-label study (NCT02760498) published recently inLancet Oncology.

Nearly half the patients (n = 34, 44%) displayed an objective response (95% Confidence Interval [CI] 32-55 of 78 patients. Ten patients (13%) experienced a complete response and 24 patients (31%) had a partial response.

Grade 3-4 treatment-emergent adverse events (AEs) were common, with nearly half the patients (n = 34, 44%) experiencing them. The most common were hypertension (n = 6, 8%) and pneumonia (n = 4, 5%). Nearly one-third of patients (n = 23, 29%) experienced serious treatment-emergent AEs.

“Our analysis shows meaningful clinical benefit in a patient population that previously had no widely accepted standard of care,” wrote the authors, led by Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center. “It strengthens the previously available evidence that supported the U.S. Food and Drug Administration’s approval of cemiplimab-rwlc for patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation, addressing a large unmet need.”

During a 2-year period, investigators enrolled 78 patients. Participants were drawn from 25 outpatient clinics in Australia, Germany, and the United States. They had locally advanced cutaneous squamous cell carcinoma without nodal or distant metastasis, ECOG performance status of 0 or 1, adequate organ function, and at least one lesion measurable by digital medical photography. Exclusion factors included autoimmune disease requiring systemic immunosuppressants, previous treatment with anti-PD-1 or anti-PD-L1 therapy, previous solid organ transplantation, or additional malignancies, including hematological cancers.

Patients received cemiplimab 3 mg/kg every 2 weeks for up to 96 weeks. In addition to a baseline biopsy, tumor biopsy samples were also collected at day 29. Patients were assessed for response every 8 weeks.

Treatment interruptions were allowed, as was treatment beyond disease progression if the patient could tolerate therapy. Dose reductions were also allowed, but patients whose required dose dropped below cemiplimab 0.3 mg/kg every 2 weeks were removed from the study.

The study’s primary endpoint was objective response as assessed by independent central review. Secondary endpoints investigator-assessed objective response, duration of response, progression-free survival (PFS) and overall survival (OS), safety and tolerability.

While 34 patients displayed an objective response by central review, the investigator assessment was higher: just over half the patients (n = 41, 53%; 95% CI 41—64). Of these, 13 patients had a complete response and 28 patients had a partial response.

By independent central review, the median duration of response had not been reached at data cutoff. The longest duration of response, 24.2 months, remains ongoing. Additionally, median PFS and OS had not been reached at data cutoff.

Independent central reviewers determined that 27 survival events occurred during the treatment period, leading the investigators to find that the estimated proportion of patients who were alive and had no disease progression at 12 months was 58% (95% CI 44-70). Regarding OS, there were 7 survival events, so the estimated proportion of patients who were alive at 12 months was 93% (95% CI 84-97). “Overall, among the activity endpoints studied, broad ranges in tumor mutational burden were seen among patients who had clinical benefit with cemiplimab and those who did not,” Migden et al wrote.

Two patients (3%) developed fatal treatment-emergent AEs. One patients developed infectious pneumonia that was determined to be unrelated to study treatment. The other patient developed aspiration pneumonia and died after 10 days. This death was considered related to study treatment.

Migden et al noted that most responses were rapid, with median observed time to response corresponding to the time of first tumor assessment. “Responses also show preliminary evidence of durability; longer follow-up analysis will better characterize durable responses,” they wrote. “In addition to the primary endpoint, the clinical benefit of cemiplimab in advanced cutaneous squamous cell carcinoma could be further demonstrated by other endpoints and long term follow-up of these patients. For example, the results for durable disease control suggest that some patients who do not meet the criteria for response might have clinical benefit.”

The investigators performed an immunohistochemistry analysis and found clinical activity with cemiplimab regardless of baseline PD-L1 TPS. They analyzed the association between median tumor mutational burden and clinical activity of cemiplimab and found a wide range of tumor mutational burden in both responders and non-responders.

Migden et al note that study limitations include the single-arm design, small number of patients, and absence of long-term data, as well as the use of a non-survival primary endpoint. “However, objective response as per independent central review was a suitable primary endpoint when viewed in the context of the secondary endpoint of duration of response,” they wrote. “Longer-term follow-up data are being collected and will further characterize the clinical activity and durability of response to cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma.”

Reference:

Migden MR, Khushalani NI, Chang ALS, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.Lancet Oncol.Published online January 14, 2020. https://doi.org/10.1016/ S1470-2045(19)30728-4