The monoclonal anti-PD-1 antibody cemiplimab (Libtayo) continued to demonstrate considerable antitumor activity and durable responses in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), according to follow-up data from a phase I trial presented at the 2018 ESMO Congress.
Follow-up results from the open-label, multicenter, ascending dose-escalation phase I trial (NCT02383212) of cemiplimab continued to show a safety profile comparable with other PD-1 inhibitors, with no new safety concerns observed.
Treatment for patients with CSCC shifted in September 2018 when cemiplimab became the first agent to receive FDA approval for the treatment of patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or radiation. The approval was based on a combined analysis of data from the phase II EMPOWER-CSCC-1 (Study 1540) trial and 2 advanced CSCC expansion cohorts from a phase I trial (Study 1423).
Across the entire population of this combined analysis, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38%-47%).2
The complete response (CR) rate was 4% and the partial response (PR) rate was 44%, and the duration of response (DOR) ranged from 1 month to over 15 months. Moreover, 61% of patients had a DOR ≥6 months.
Although the disease has a surgical cure rate upwards of 95%, there are an estimated 3932 to 8791 disease-related deaths in the United States in 2012.
In Europe, there are currently no approved systemic therapies to patients with advanced CSCC, leaving an unmet need for those with metastatic disease or those with locally advanced disease that is no longer amenable to surgery or radiation therapy.
For this cohort of the phase I trial, investigators sought to characterize the safety, tolerability, and efficacy of cemiplimab. To be eligible for enrollment, patients had to have an ECOG performance status of 0 or 1, adequate organ function, and at least 1 lesion measurable by RECIST criteria.
Those with any ongoing or recent autoimmune disease requiring systemic immunosuppression within the past 5 years, those with active brain metastases, or those with invasive malignancies within the past 5 years were ineligible to enroll, as were those who had been treated with immunosuppressive doses of steroids (>10 mg prednisone daily or equivalent), systemic treatment within 4 weeks of their initial dose of cemiplimab, those with a history of solid organ transplant, or those with primary tumors of the lip or eyelid.
A total of 26 patients with metastatic CSCC (n = 10) or locally and/or regionally advanced CSCC (n = 16) were enrolled in the trial. All patients were considered ineligible candidates for surgery in that they experienced recurrent disease after 2 or more surgical operations with an expectation that curative resection would be unlikely and/or if substantial morbidity or deformity from a surgical procedure was expected. The median age was 73 years old.
Patients were administered 3 mg/kg of intravenous cemiplimab bi-weekly for up to 48 weeks. At the time of data cut-off on January 20, 2018, 12 patients (46.2%) completed the planned treatment, while 14 (53.8%) had discontinued treatment, mainly due to disease progression (n = 7).
The median number of administered doses of cemiplimab was 16 (range: 2-44), while the median duration of exposure was 36.0 weeks (range: 4.0-86.7). Two patients entered the retreatment phase of the trial at the time of data cut-off, and 1 of these patients had an extended retreatment phase, which consisted of continued cemiplimab exposure for 86.7 weeks. The median duration of follow-up at the time of data cut-off was 11.9 months (range: 1.1-18.2).
Updated efficacy findings showed that the ORR was still 50.0% (95% CI, 29.9%-70.1%), while the durable disease control rate was 57.7% (95% CI, 36.9%-76.6%). Rapid, deep, and durable target lesion reductions were reported in the majority of patients who underwent at least 1 tumor assessment while receiving treatment. At the time of data cut-off, the median DOR had not been reached.
Treatment-emergent adverse events (TEAEs) of any grade were observed in all patients, regardless of attribution. Investigator-assessed treatment-related TEAEs were noted in 16 patients (61.5%), with 4 patients (15.4%) experiencing the following grade ≥3 AEs: adrenal insufficiency, asthenia, increased alanine aminotransferase, increased aspartate aminotransferase, and maculo-papular rash.
Fatigue (26.9%), arthralgia, diarrhea, hypothyroidism, muscle weakness, and macular-papular rash (all 7.7% each), were observed as the most common treatment-associated TEAEs. Two patients discontinued treatment with cemiplimab; 1 developed grade 3 rash and grade 2 cough following 3 doses of the drug, while another patient developed grade 2 muscular weakness after receiving 5 doses.
The investigators concluded that the primary analysis of the CSCC cohort combined with the prespecified interim analysis of the locally advanced cohort from the ongoing phase II trial (NCT02760498) further evidences the significant antitumor activity and durable response achieved with the use of cemiplimab in patients with advanced CSCC.
- Owonlkoko TK, Papadopoulos KP, Johnson ML, et al. Phase I study of cemiplimab, a human monoclonal anti-PD-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): longer follow-up efficacy and safety data [published online ahead of print October 23, 2018]. Ann Oncol. doi: 10.1093/annonc/mdy289.048.
- Rischin CD, Migden MR, Chang A, et al. Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC). J Clin Oncol. 2018;36 (suppl; abstr 9519). doi: 10.1200/JCO.2018.36.15_suppl.9519.