Pembrolizumab for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC): Efficacy and safety results from the phase II KEYNOTE-629 study

Grob, J.J.; Mendoza, René González; Basset-Séguin, Nicole; Vornicova, Olga; Schachter, Jacob; Joshi, Abhishek; Meyer, Nicolas; Grange, Florent; Piulats, Josep M.; Bauman, Jessica R.; Zhang, P.; Gümüşçü, Burak; Swaby, Ramona F.; Hughes, Benjamin

doi:10.1093/annonc/mdz394.069

Cited by 12 publications

(24 citation statements)

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“…In recent congress proceedings, pembrolizumab demonstrated ORR of 34.3% (n=105; median follow-up of 9.5 months) in patients with recurrent/mCSCC. 29 These data further support the clinical activity of PD-1 checkpoint inhibitors in advanced CSCC.…”

Section: Discussionmentioning

confidence: 54%

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Rischin

Migden

Lim

et al. 2020

J Immunother Cancer

138

146

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BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

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Section: Discussionmentioning

confidence: 54%

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Rischin

Migden

Lim

et al. 2020

J Immunother Cancer

138

146

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“…Subsequent research based on approximately 1 year of additional follow-up from the Phase II cemiplimab trial indicated that median overall survival (OS) has not been reached and the estimated OS at 24 months was 73.3% (95% CI: 66.1-79.2) [31]. In 2020, pembrolizumab, another PD-1 inhibitor, was approved by the FDA for advanced CSCC based on data from the KEYNOTE-629 study [32].…”

Section: Graphical Abstractmentioning

confidence: 99%

“…Searches through other sources resulted in a total of 165 citations categorized as additional records identified through other sources. Overall, 42 citations, corresponding to 27 studies were included [22][23][24][25]32,. The search of the WHO ICTRP found 96 studies, 25 of which were completed (n = 4) or ongoing (n = 21) clinical trials that met the eligibility criteria and were not already captured in the main search.…”

Section: Systematic Literature Reviewmentioning

confidence: 99%

Comparative Efficacy of Cemiplimab Versus Other Systemic Treatments for Advanced Cutaneous Squamous Cell Carcinoma

Keeping

Chen

et al. 2020

Future Oncol.

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Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07–0.52) and progression-free survival (hazard ratios range: 0.30–0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.

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“…The use of PD-1/PD-L1 immune check point inhibitor is generally well tolerated and publications of prospective phase 2 studies [ 19 , 20 ] on cemiplimab have shown impressive response of patients with recurrent advanced/metastatic cSCC being sensitive to PD-1 blockade. The survival benefit of adding immunotherapy to chemoradiation is also evident in the setting of locally advanced non-small cell lung cancer as shown in a randomized controlled trial [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma

et al. 2021

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Background Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort. Methods Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored. Discussion CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC. Trial registration: Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)

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Pembrolizumab for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC): Efficacy and safety results from the phase II KEYNOTE-629 study

Cited by 12 publications

References 0 publications

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Comparative Efficacy of Cemiplimab Versus Other Systemic Treatments for Advanced Cutaneous Squamous Cell Carcinoma

A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma

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