Quality of life in cemiplimab-treated patients with locally advanced basal cell carcinoma in a Phase II clinical trial.

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC). Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles. Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue. Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue.Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.

Locally advanced basal cell carcinoma (laBCC) is a type of skin cancer that has the potential to invade surrounding tissues including bone, cartilage, nerve and muscle. Cemiplimab-rwlc is approved in the US for patients with laBCC following a therapy called hedgehog inhibitor (HHI) treatment or for whom HHIs are not appropriate. In a Phase II clinical trial, intravenous (in the vein) cemiplimab 350 mg every 3 weeks for up to nine treatment cycles resulted in clinically meaningful antitumor activity in patients with laBCC who progressed on or were intolerant to HHIs.This analysis evaluated health-related quality of life, symptom burden, emotions and functional status in these patients using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires. Baseline scores (scores at the start of the clinical trial) showed moderate to high levels of functioning and low symptom burden that, except for fatigue, were maintained or improved over the course of cemiplimab treatment. These results show that despite the presence of fatigue, health-related quality of life and functional status were maintained with cemiplimab across the study duration.

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial.

BACKGROUND: Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy. METHODS: We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years and with an Eastern Cooperative Oncology Group performance status of 0 or 1) with a histologically confirmed diagnosis of metastatic basal cell carcinoma (group 1) or locally advanced basal cell carcinoma (group 2) who had progressed on or were intolerant to previous HHI therapy were enrolled. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until progression or unacceptable toxicity. The primary endpoint was objective response by independent central review. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. The primary analysis is reported only for group 2; group 1 data have not reached maturity and will be reported when the timepoint, according to the statistical analysis plan, has been reached. This study is registered with ClinicalTrials.gov, NCT03132636, and is no longer recruiting new participants. FINDINGS: Between Nov 16, 2017, and Jan 7, 2019, 84 patients were enrolled and treated with cemiplimab. At data cutoff on Feb 17, 2020, median duration of follow-up was 15 months (IQR 8-18). An objective response per independent central review was observed in 26 (31%; 95% CI 21-42) of 84 patients, including two partial responses that emerged at tumour assessments before the data cutoff and were confirmed by tumour assessments done subsequent to the data cutoff. The best overall response was five (6%) patients with a complete response and 21 (25%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 40 (48%) of 84 patients; the most common were hypertension (four [5%] of 84 patients) and colitis (four [5%]). Serious treatment-emergent adverse events occurred in 29 (35%) of 84 patients. There were no treatment-related deaths. INTERPRETATION: Cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

LESSONS LEARNED: Cemiplimab in combination with radiation therapy, cyclophosphamide, and granulocyte macrophage colony-stimulating factor did not demonstrate efficacy above what can be achieved with other PD-1 inhibitor monotherapies in patients with refractory and metastatic head and neck squamous cell carcinoma. The safety profile of cemiplimab combination therapy was consistent with previously reported safety profiles of cemiplimab monotherapy. No new safety signal was observed. BACKGROUND: Refractory and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) generally does not respond to PD-1 inhibitor monotherapy. Cemiplimab is a human anti-PD-1 monoclonal antibody. An expansion cohort enrolled patients with R/M HNSCC in a phase I study combining cemiplimab plus radiation therapy (RT), cyclophosphamide, and granulocyte macrophage colony-stimulating factor (GM-CSF). METHODS: Patients with R/M HNSCC refractory to at least first-line therapy and for whom palliative RT is clinically indicated received cemiplimab plus RT, cyclophosphamide, and GM-CSF. The co-primary objectives were the safety, tolerability, and efficacy of cemiplimab plus RT, cyclophosphamide, and GM-CSF in 15 patients with R/M HNSCC. RESULTS: Fifteen patients were enrolled. Patients discontinued treatment due to progression of disease. The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (40.0%), constipation (26.7%), and asthenia, dyspnea, maculo-papular rash, and pneumonia (each 20%). The only grade ≥3 TEAE that occurred in two patients was pneumonia (13.3%). By investigator assessment, there was one partial response (6.7%); disease control rate was 40.0% (95% confidence interval [CI], 16.3-67.7; five patients with stable disease); seven patients had progressive disease, and two were not evaluable. Median progression-free survival by investigator assessment was 1.8 months (95% CI, 1.7-4.7). CONCLUSION: The regimen demonstrated tolerability but not efficacy above that which can be achieved with anti-PD-1 inhibitor monotherapy for R/M HNSCC.

PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. METHODS: We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. RESULTS: In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. CONCLUSIONS: Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort.

OBJECTIVES: Blockade of programmed cell death-1 (PD-1) and its ligand (PD-L1) has transformed the treatment of NSCLC. In a first-in-human, Phase 1, dose escalation and cohort expansion study, cemiplimab, a monoclonal antibody directed against PD-1, was evaluated for the treatment of patients with advanced solid tumors (NCT02383212). Here, we report results in patients with advanced NSCLC from the dose expansion cohort. MATERIALS AND METHODS: Immune-checkpoint inhibitor naive patients with advanced NSCLC (stage III/IV), irrespective of PD-L1 status, who had progressed after, or were refractory to first- or later-line therapy were enrolled and received cemiplimab 200 mg every 2 weeks intravenously for up to 48 weeks. Primary study objectives were to assess safety and tolerability, and to evaluate clinical activity of cemiplimab. RESULTS: Twenty patients with NSCLC were enrolled. Median age was 64.0 years (range: 50-82); 65.0 % were male; 80.0 % had an ECOG performance status of 1; 60.0 % had a histology of adenocarcinoma. Median number of prior lines of systemic therapy was 2 (range: 1-4). Median duration of follow-up was 7.0 months (range: 1.0-18.2). All patients experienced ≥1 treatment-emergent adverse event (TEAE) of any grade. Most common TEAEs were arthralgia, asthenia, cough, and dyspnea (each 4/20; 20.0 %). Grade ≥3 TEAEs occurred in 60.0 % (12/20) of patients. Of patients with measurable disease per independent central review (ICR), five had partial response (PR), four had stable disease (SD) and 10 had progressive disease. Objective response rate (ORR; complete response + PR) was 25.0 % (95 % CI: 8.7-49.1 %). Duration of response exceeded 8 months in four of the five responding patients at the time of data cut-off (April 30, 2019). The disease control rate per ICR (ORR + SD) was 50.0 % (95 % CI: 27.2-72.8 %). CONCLUSION: Cemiplimab showed an acceptable safety profile and demonstrated antitumor activity in pretreated patients with NSCLC.