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Purpose <p>Pharmacokinetics, pharmacodynamics, safety, and efficacy of subcutaneous cetrelimab were assessed in Parts (P)3 and 4 of the phase I LUC1001 study in patients with advanced/refractory solid tumors who progressed&#xa0;on&#xa0;or wereineligible for standard treatment and had no prior PD-1/PD-L1/PD-L2 treatment.</p> Methods <p>In P3, low-concentration cetrelimab (30&#xa0;mg/mL) was administered subcutaneously&#xa0;at 600&#xa0;mg with a 6-week interval between doses 1 and 2, then every 3&#xa0;weeks (Q3W). Based on P3 pharmacokinetic and safety findings, high-concentration cetrelimab (150&#xa0;mg/mL) was administered subcutaneously&#xa0;at a 900&#xa0;mg loading dose followed by 600&#xa0;mg Q3W in P4.</p> Results <p>Among 30 enrolled patients (P3, n = 11; P4, n = 19), median age was 54.5y; 76.7% received ≥ 3 prior lines of therapy. Median duration of treatment was 2.1mo. Treatment-related adverse events (AEs) occurred in 70% of patients, including 23.3% with grade ≥ 3 treatment-related AEs and 30.0% immune-related AEs; no treatment-related serious AEs or systemic infusion-related reactions occurred. After 3.7mo median follow-up, 2 patients (6.7%) achieved durable responses and&#xa0;4 patients (13.3%) had stable disease for ≥ 24&#xa0;weeks. Pharmacokinetic data showed that adding a 900&#xa0;mg loading dose to the 600&#xa0;mg Q3W subcutaneous&#xa0;regimen shortened the time to reach target recommended phase 2 dose (RP2D) exposures, making it a suitable intravenous alternative. Maximum PD-1 receptor occupancy was achieved with both formulations. Anti-cetrelimab antibodies were detected in 4 patients (13.3%); none were neutralizing.</p> Conclusions <p>RP2D of subcutaneous cetrelimab was established as a loading dose of 900&#xa0;mg followed by 600&#xa0;mg Q3W. Subcutaneous cetrelimab demonstrated characteristics consistent with prior characterization of intravenous cetrelimab.</p> <p><i>Trial registration</i> NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016–002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.</p>

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A phase I study evaluating subcutaneous administration of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced solid malignancies

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  • 发表日期：

    2026年6月18日

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  • Piotr Rutkowski,
  • Dariusz M. Kowalski,
  • Victor Moreno,
  • Aitana Calvo,
  • Fiona Thistlethwaite,
  • Ruth Plummer,
  • Douglas Steinbach,
  • John Loffredo,
  • Sydney Akapeme,
  • Daniel Jonathan,
  • Vinod Philip,
  • Angela Girvin,
  • Shalaka Hampras,
  • Peter Hellemans,
  • Iurie Bulat

摘要

Purpose

Pharmacokinetics, pharmacodynamics, safety, and efficacy of subcutaneous cetrelimab were assessed in Parts (P)3 and 4 of the phase I LUC1001 study in patients with advanced/refractory solid tumors who progressed on or wereineligible for standard treatment and had no prior PD-1/PD-L1/PD-L2 treatment.

Methods

In P3, low-concentration cetrelimab (30 mg/mL) was administered subcutaneously at 600 mg with a 6-week interval between doses 1 and 2, then every 3 weeks (Q3W). Based on P3 pharmacokinetic and safety findings, high-concentration cetrelimab (150 mg/mL) was administered subcutaneously at a 900 mg loading dose followed by 600 mg Q3W in P4.

Results

Among 30 enrolled patients (P3, n = 11; P4, n = 19), median age was 54.5y; 76.7% received ≥ 3 prior lines of therapy. Median duration of treatment was 2.1mo. Treatment-related adverse events (AEs) occurred in 70% of patients, including 23.3% with grade ≥ 3 treatment-related AEs and 30.0% immune-related AEs; no treatment-related serious AEs or systemic infusion-related reactions occurred. After 3.7mo median follow-up, 2 patients (6.7%) achieved durable responses and 4 patients (13.3%) had stable disease for ≥ 24 weeks. Pharmacokinetic data showed that adding a 900 mg loading dose to the 600 mg Q3W subcutaneous regimen shortened the time to reach target recommended phase 2 dose (RP2D) exposures, making it a suitable intravenous alternative. Maximum PD-1 receptor occupancy was achieved with both formulations. Anti-cetrelimab antibodies were detected in 4 patients (13.3%); none were neutralizing.

Conclusions

RP2D of subcutaneous cetrelimab was established as a loading dose of 900 mg followed by 600 mg Q3W. Subcutaneous cetrelimab demonstrated characteristics consistent with prior characterization of intravenous cetrelimab.

Trial registration NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016–002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.