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Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors.

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Author information

Affiliations

  • 1. South Texas Accelerated Research Therapeutics (START), San Antonio, Texas.
      Authors
    • Patnaik A 1
    • Rasco D 1
    • Papadopoulos KP 1
    • Beeram M 1
    • Drengler R 1
    • Smith L 1
    • Espino G 1
    • Tolcher AW 1
    (8 authors)
  • 2. Merck & Co., Inc., Kenilworth, New Jersey.
      Authors
    • Kang SP 2
    • Elassaiss-Schaap J 2
    • Chen C 2
    • Gergich K 2
    • Delgado L 2
    • Lindia JA 2
    • Li XN 2
    • Pierce RH 2
    • Yearley JH 2
    • Wu D 2
    • Laterza O 2
    • Lehnert M 2
    • Iannone R 2
    (13 authors)
  • 3. University of California, San Francisco, San Francisco, California.
      Authors
    • Daud A 3
    (1 author)

ORCIDs linked to this article

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 14 May 2015, 21(19):4286-4293
https://doi.org/10.1158/1078-0432.ccr-14-2607 PMID: 25977344 

Abstract 

Purpose

This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in patients with advanced solid tumors.

Experimental design

In a 3 + 3 dose escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg intravenously every 2 weeks until progression or intolerable toxicity. Seven additional patients received 10 mg/kg every 2 weeks. Thirteen patients participated in a 3-week intrapatient dose escalation (dose range, 0.005-10 mg/kg) followed by 2 or 10 mg/kg every 3 weeks. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Results

No dose-limiting toxicities were observed. Maximum administered dose was 10 mg/kg every 2 weeks. One patient with melanoma and one with Merkel cell carcinoma experienced complete responses of 57 and 56+ weeks' duration, respectively. Three patients with melanoma experienced partial responses. Fifteen patients with various malignancies experienced stable disease. One patient died of cryptococcal infection 92 days after pembrolizumab discontinuation, following prolonged corticosteroid use for grade 2 gastritis considered drug related. Pembrolizumab exhibited pharmacokinetic characteristics typical of humanized monoclonal antibodies. Maximum serum target engagement was reached with trough levels of doses greater than or equal to 1 mg/kg every 3 weeks. Mechanism-based translational models with a focus on intratumor exposure prediction suggested robust clinical activity would be observed at doses ≥2 mg/kg every 3 weeks.

Conclusions

Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. The lowest dose with full potential for antitumor activity was 2 mg/kg every 3 weeks.

Full text links 

Read article at publisher's site: https://doi.org/10.1158/1078-0432.ccr-14-2607

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