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•Cemiplimab monotherapy was evaluated in pretreated patients with advanced NSCLC.•Cemiplimab showed substantial antitumor activity, with durable responses observed.•The majority of ...TEAEs observed with cemiplimab treatment were Grades 1–2.•No unexpected safety signals were observed.•Cemiplimab is a promising therapy option for patients with pretreated advanced NSCLC.
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.
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.
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 %).
Cemiplimab showed an acceptable safety profile and demonstrated antitumor activity in pretreated patients with NSCLC.
BackgroundHHIs, vismodegib and sonidegib, are approved for treatment of patients with mBCC or locally advanced BCC who are not candidates for surgery or radiation. There is no approved option for ...patients who progress on or are intolerant to HHIs. Cemiplimab is an anti-programmed cell death-1 monoclonal antibody approved for treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Here we present the prespecified interim analysis of the mBCC cohort from the pivotal Phase 2, non-randomized, multi-center study of cemiplimab in patients with advanced BCC who discontinued HHI therapy due to disease progression, intolerance, or no better than stable disease after 9 months (NCT03132636).MethodsPatients with mBCC (nodal and/or distant) received cemiplimab 350 mg intravenously every 3 weeks; interim analysis included patients with the opportunity to be followed for approximately 57 weeks. The primary endpoint was objective response rate (ORR) per independent central review (ICR). Secondary objectives included assessment of safety and tolerability, estimation of duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsIn this interim efficacy analysis of 28 patients, 82.1% were males and median age was 65.5 years (range 38−90). Six patients had a partial response, per ICR, for an ORR of 21.4% (95% CI, 8.3, 41.0). ORR per investigator assessment was 28.6% (95% CI, 13.2, 48.7). Among responders, observed DOR was 9−23 months. Median time to response per ICR was 3.2 months (range, 2.1−10.5). Median Kaplan–Meier (KM) estimation of PFS was 8.3 months. Median DOR had not been reached and median KM estimation of OS was 25.7 months. All six responses had observed durations of at least 8 months. The disease control rate was 67.9% (95% CI, 47.6, 84.1).The most common treatment emergent adverse events (TEAEs) regardless of attribution were fatigue (50.0%), diarrhea (35.7%), pruritus (25.0%), and constipation (25.0%). Hypertension (n=2) was the only Grade ≥3 TEAE regardless of attribution occurring in ≥2 patients. TEAEs leading to death occurred in one (3.6%) patient who died from staphylococcal pneumonia, considered unrelated to study treatment.ConclusionsThis interim analysis demonstrates that cemiplimab is the first agent to provide clinically meaningful anti-tumor activity, including durable responses, in patients with mBCC after progression or intolerance on HHI therapy.AcknowledgementsEditorial acknowledgment: Medical writing support was provided by Cindi Hoover, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.Ethics ApprovalThe study protocols and all amendments were approved by the institutional review board at each participating study site. The study was conducted in accordance with the principles of the Declaration of Helsinki and with Good Clinical Practice guidelines as defined by the International Conference on Harmonization. All patients provided written informed consent before enrollment.
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.
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.
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.
Cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy.
Regeneron Pharmaceuticals and Sanofi.
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.
Cemiplimab in combination with radiation therapy, cyclophosphamide, and granulocyte macrophage colony-stimulating factor (GM-CSF) 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.
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).
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 (pts) with R/M HNSCC.
Fifteen patients were enrolled. Patients discontinued treatment due to progression of disease. The most common treatment-emergent adverse events (TEAEs) of any grade (Gr) were fatigue (40.0%), constipation (26.7%), and asthenia, dyspnea, maculo-papular rash, and pneumonia (each 20%). The only Gr ≥3 TEAE that occurred in 2 pts was pneumonia (13.3%). By investigator-assessment, there was 1 partial response (6.7%); disease control rate was 40.0% (95% CI: 16.3-67.7; 5 with stable disease); 7 patients had progressive disease and 2 were not evaluable. Median progression-free survival by investigator-assessment was 1.8 months (95% CI: 1.7-4.7).
The regimen demonstrated tolerability but not efficacy above that which can be achieved with anti-PD-1 inhibitor monotherapy for R/M HNSCC.
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