Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma

Ahmed, Salmaan; Petersen, Erik; Patel, Ravi B.; Migden, Michael R.

doi:10.1080/17512433.2019.1665026

Cited by 60 publications

(49 citation statements)

References 26 publications

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“…Although there are certainly differences among the drugs and their target binding (eg, nivolumab and pembrolizumab bind different regions of PD‐1 20 ), the ultimate mechanistic objective is to block the interaction between PD‐1 and PD‐L1. The molecular structures of the three anti‐PD‐1 inhibitors (cemiplimab‐rwlc, pembrolizumab and nivolumab) are all based on the immunoglobulin G4 family (IgG4) and are identical in their mechanism of action with very similar PK and PD 9,21,22 . Cemiplimab‐rwlc, pembrolizumab and nivolumab each demonstrate time‐dependent changes in PK, specifically the clearance pathways (target binding, protein catabolism, etc), to strikingly similar degrees 4,23 .…”

Section: Potential Opportunities For Cost Savingsmentioning

confidence: 99%

Opportunities for using in silico‐based extended dosing regimens for monoclonal antibody immune checkpoint inhibitors

Peer

Goldstein

Goodell

et al. 2020

Brit J Clinical Pharma

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Therapeutic drug monitoring (TDM) involves frequent measurements of drug concentrations to ensure levels remain within a therapeutic window, and it is especially useful for drugs with narrow therapeutic indices or extensive interindividual pharmacokinetic variability. This technique has never been applied to immuno‐oncology drugs, but, given recent examinations of clinical data (both exposure and response) on a number of these drugs, further investigations into TDM may be justified to reduce costs as well as potentially reducing the severity and/or duration of immune‐related adverse events. Specifically, all but one of the approved PD‐1 and PD‐L1 inhibitors (pembrolizumab, nivolumab, cemiplimab‐rwlc, atezolizumab, avelumab, durvalumab) have been shown to exhibit a plateaued exposure‐response (E‐R) curve at doses evaluated extensively to date, as well as time‐dependent changes in drug exposure. Furthermore, responders have a greater decrease in drug clearance over time and would, therefore, have supratherapeutic serum concentrations. With frequent trough measurements, it is possible to use pharmacokinetic modelling and simulation to estimate drug clearance via Bayesian methods. Based on patient‐specific estimates for clearance, optimal alternative dosing strategies can be simulated to lower drug and cost burden yet maintain therapeutic levels, especially as the clearance of the drug decreases over time. This review will comprehensively discuss each of the FDA approved PD‐1, PD‐L1/2 and CTLA‐4 inhibitors regarding their indications and current recommended dosing, with evidence supporting the investigation of these types of TDM strategies.

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Section: Potential Opportunities For Cost Savingsmentioning

confidence: 99%

Opportunities for using in silico‐based extended dosing regimens for monoclonal antibody immune checkpoint inhibitors

Peer

Goldstein

Goodell

et al. 2020

Brit J Clinical Pharma

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“…Low-risk HPV types include types 6, 11, 42, 43, and 44. High-risk HPV types include types 16,18,31,33,34,35,39,45,51,52,56,58,59,66,68, and 70 [25,26]. Vaccines against HPV are essential to prevent the development of CC and other gynecologic cancers and to protect against HPV types 16 and 18.…”

Section: Risk Factors and Clinical Featuresmentioning

confidence: 99%

“…Currently, several clinical trials are assessing the clinical activity and safety of PD-L1 inhibitor monotherapy or in combination with chemotherapeutic agents such as bevacizumab, paclitaxel or carboplatin, cobimetinib (the mitogen-activated protein kinase enzymes inhibitor) [65], and platinum-based chemotherapy in OC (Table 4) [66,67]. The KGOG 3045 study aims to investigate durvalumab therapy in platinum-resistant recurrent OC patients [65,68].…”

Section: Monotherapy or Combination Therapy With Pd-l1 Inhibitors In mentioning

confidence: 99%

“…A total of 264 patients will participate in this phase 1/2 study. The primary endpoint of this trial is to evaluate the preliminary efficacy of monotherapy with REGN4018 and the combination of REGN4018 with cemiplimab; the secondary endpoint will include will be to estimate response length, disease control rate, and PFS (Table 3) [66].…”

Section: Combination Therapy Of Pd-1 Inhibitors With Chemotherapy Andmentioning

confidence: 99%

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The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers

Kooshkaki

Derakhshani

Safarpour

et al. 2020

IJMS

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Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host–tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.

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“…We report a case of renal endothelialitis in the setting of treatment with cemiplimab, an intravenous programmed cell death–1 receptor monoclonal antibody recently approved for treatment of programmed cell death–1 receptor advanced invasive squamous cell carcinoma. 7 …”

Section: Introductionmentioning

confidence: 99%