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A phase I study of IMC-001, a PD-L1 blocker, in patients with metastatic or locally advanced solid tumors

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Summary

Introduction IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 (programmed death-ligand 1). This study evaluated the safety, pharmacokinetics, and pharmacodynamics of IMC-001 in patients with advanced solid tumors. Materials and Methods This open-labeled phase I study used a standard 3 + 3 dose-escalation design, with doses ranging from 2 to 20 mg/kg. IMC-001 was administered intravenously every 2 weeks until disease progression or unacceptable toxicity. The dose-limiting toxicity window was defined as 21 days from the first dose. Results Fifteen subjects were included in 5 dose-escalation cohorts. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common adverse events (AEs) were general weakness, decreased appetite, fever, and cough. No grade 4 or 5 treatment emergent AEs were reported during the study. One subject in the 2 mg/kg cohort showed grade 2 immune-induced thyroiditis and diabetes mellitus suspected to be related to IMC-001. Over the dose range of 2–20 mg/kg IMC-001, the AUC0–14d, AUC0—∞, and Cmax generally increased in a dose-proportional manner for each step of dose escalation. Of the 15 enrolled patients, 1 subject with rectal cancer showed a partial response, and the disease control rate was 33.3%. Conclusions IMC-001 demonstrated a favorable safety profile up to 20 mg/kg administered intravenously every 2 weeks and showed preliminary efficacy in patients with advanced solid tumors. Based on pharmacokinetic and pharmacodynamic data, 20 mg/kg was selected as the recommended phase II dose. Clinical trial identification NCT03644056 (date of registration: August 23, 2018).

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Data availability

The data that support the findings of this study are available on request from the corresponding author Dr. Park. The data are not publicly available due to information that could compromise research participant consent.

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Acknowledgements

We thank the participating patients, their family members, and all researchers involved in this study.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

    Bhumsuk Keam, Chan-Young Ock, Tae Min Kim & Do-Youn Oh

  2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Bhumsuk Keam, Tae Min Kim & Do-Youn Oh

  3. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Won Ki Kang, Yeon Hee Park, Jeeyun Lee & Young Suk Park

  4. ImmuneOncia Therapeutics Inc., Seongnam, South Korea

    Ji Hye Lee, Yoen Hee Ahn, Hyeon Ju Kim, Sook Kyung Chang, Jihyun Park, Ji Yea Choi & Yun Jeong Song

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  1. Bhumsuk Keam
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Contributions

This study was directed and coordinated by B Keam and YS Park, as the principal investigators, provided conceptual and technical guidance for all aspects of the study and drafted the manuscript. C-Y Ock, TM Kim, D-Y Oh, WK Kang, YH Park, J LEE participated the study as the co-investigators and helped to draft the manuscript. JH Lee, YH Ahn, HJ Kim and YJ Song planned and managed the study operation and analyzed clinical data and drafted the manuscript. SK Chang, J Park, JY Choi carried out the biomarker studies and drafted biomarker part of the manuscript. All authors reviewed the final manuscript.

Corresponding author

Correspondence to Young Suk Park.

Ethics declarations

Ethics approval

1. H-1801-042-913

2. SMC 2018–01–007-001

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Informed consent for the publication of any associated data was obtained from all individual participants in the study.

Conflict of interest

Ji Hye Lee, Yoen Hee Ahn, Hyeon Ju Kim, Sook Kyung Chang, Jihyun Park, Ji Yea Choi and Yun Jeong Song are full-time employees of ImmuneOncia Therapeutics Inc.

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Keam, B., Ock, CY., Kim, T.M. et al. A phase I study of IMC-001, a PD-L1 blocker, in patients with metastatic or locally advanced solid tumors. Invest New Drugs 39, 1624–1632 (2021). https://doi.org/10.1007/s10637-021-01078-6

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