Dataset Information

Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies.

ABSTRACT:

Purpose

Part 1 of this two-part, open-label, Phase 1 study (NCT03233139) assessed the safety, tolerability, pharmacokinetics, immunogenicity, and clinical activity of cemiplimab in Japanese patients with advanced malignancies.

Methods

Patients received cemiplimab 250 mg (n?=?6) or 350 mg (n?=?7) every 3 weeks intravenously for up to 108 weeks in Part 1. Tumor responses were assessed by investigators every 9 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1.

Results

Of 13 patients enrolled, median age was 62 years (range 33-75) and eight patients were female. Median duration of cemiplimab exposure was 13.1 weeks (range 3.0?113.6). At the time of data cut-off, 11 patients (84.6%) had discontinued treatment (majority due to disease progression: n?=?8, 61.5%). The most common treatment-emergent adverse events (TEAEs) of any grade were contact dermatitis, rash, and viral upper respiratory tract infection (each n?=?3, 23.1%). Five grade???3 TEAEs were reported in four patients: autoimmune colitis, dehydration, hyponatremia, hypophosphatemia, and muscular weakness. No dose-limiting toxicities were reported and no TEAEs led to death. Cemiplimab concentrations in serum were consistent with previously reported pharmacokinetic characteristics of cemiplimab. No anti-drug antibodies were detected in serum. Objective response rate [ORR; complete response?+?partial response (PR)] was 30.8% (four PR) and disease control rate [ORR?+?stable disease (SD)] was 46.2% (6/13; two SD).

Conclusion

Cemiplimab exhibited antitumor activity in Japanese patients with advanced malignancies. The safety profile was comparable to those previously reported for cemiplimab and other PD-1 inhibitors.

Trial registration

NCT03233139 at ClinicalTrials.gov.

SUBMITTER: Kitano S

PROVIDER: S-EPMC7801352 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies.

Kitano Shigehisa S Shimizu Toshio T Koyama Takafumi T Ebata Takahiro T Iwasa Satoru S Kondo Shunsuke S Shimomura Akihiko A Fujiwara Yutaka Y Yamamoto Noboru N Paccaly Anne A Li Siyu S Rietschel Petra P Sims Tasha T

Cancer chemotherapy and pharmacology 20201104 1

<h4>Purpose</h4>Part 1 of this two-part, open-label, Phase 1 study (NCT03233139) assessed the safety, tolerability, pharmacokinetics, immunogenicity, and clinical activity of cemiplimab in Japanese patients with advanced malignancies.<h4>Methods</h4>Patients received cemiplimab 250 mg (n = 6) or 350 mg (n = 7) every 3 weeks intravenously for up to 108 weeks in Part 1. Tumor responses were assessed by investigators every 9 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1.< ...[more]

PMID: 33146741

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Project description:BackgroundInhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have represented a novel approach for the management of advanced non-small cell lung cancer (NSCLC). In this study, we aimed to estimate five anti-PD-1/L1 agents (nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab) using network meta-analyses (NMAs) and the Bayesian method to provide suggestions for advanced NSCLC treatments.MethodsWe searched PubMed, Web of Science, Embase, and the Wiley Online Library for eligible studies published up to March 2020. Both pairwise analyses and NMAs were conducted with clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate, and the incidences of adverse events. Results were presented in several patient populations according to treatment lines and PD-L1 status.ResultsNineteen randomized clinical trials (RCTs) involving 11,456 patients were included in our study. PD-1/L1 inhibitors showed significant benefits over chemotherapies in OS regardless of tumor PD-L1 status [first-line settings: OS =0.85, 95% CI (0.77, 0.94), I2=37%; second- or further-line settings: OS =0.77, 95% CI (0.71, 0.84), I2=37%]. The combined regimen of pembrolizumab and chemotherapy stood out to be the most effective and safest for patients in the first-line settings. Pembrolizumab monotherapy was showed to be the best especially for patients with PD-L1 ≥50%. In the subsequent-line settings, nivolumab ranked the best in improving the survival of patients, and durvalumab had the greatest effect in tumor shrinkage. Atezolizumab, followed by nivolumab, ranked the safest in reducing adverse events, whereas durvalumab was showed with the largest side effects among the five inhibitors.ConclusionsThe combination of pembrolizumab with chemotherapy is suitable for advanced NSCLC patients who have not received any systematic treatments before, and pembrolizumab monotherapy should also be considered, especially for patients with highly-expressed PD-L1 (≥50%). Nivolumab is the best option for patients with advanced NSCLC whose tumors have progressed following chemotherapies or combined modalities of treatments including chemotherapy. However, our results need to be further validated in future head-to-head clinical trials.

Dataset Information

Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies.

Purpose

Methods

Results

Conclusion

Trial registration

Publications

Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies.

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