Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Cergutuzumab Amunaleukin in Combination with Atezolizumab in Patients with Carcinoembryonic Antigen-Positive Advanced/Metastatic Solid Tumors.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Melero Ignacio, Tabernero Josep, Steeghs Neeltje, Robbrecht Debbie G J, Peters Solange, Rizvi Naiyer A, O'Reilly Eileen M, Calvo Emiliano, Eefsen Rikke L, Leighl Natasha, Cervantes Andres, Hafez Navid, Habigt Christin, Andersson Emilia, Dejardin David, Rossmann Eva, Martinez Quetglas Iris, Babitzki Galina, Duarte José, Adessi Celine, Boetsch Christophe, Evers Stefan, Charo Jehad, Teichgräber Volker, Lassen Ulrik
Аннотация
PURPOSE: Cergutuzumab amunaleukin (CA) is an immunocytokine comprising a variant form of interleukin 2 (IL2) [constructed to avoid CD25 binding and regulatory T-cell (Treg) stimulation] fused to a carcinoembryonic antigen (CEA)-targeted antibody. This phase Ib open-label, multicenter dose-escalation and -expansion study (NCT02350673) evaluated the safety, activity, pharmacokinetics, and pharmacodynamics of CA plus atezolizumab in patients with advanced/metastatic CEA-positive solid tumors.
PATIENTS AND METHODS: Patients received escalating doses of CA (6-20/25 mg) with fixed dosages of atezolizumab (840 mg) every 2 weeks or escalating dosages of CA weekly (10-15/20 mg) with fixed dosages of atezolizumab (1,200 mg) every 3 weeks. Primary objectives include maximum tolerated dose (MTD), recommended dose for expansion (RDE), and safety.
RESULTS: Twenty-four patients were randomized to receive CA plus atezolizumab every 2 weeks and 45 patients to CA weekly plus atezolizumab every 3 weeks. A subgroup of patients (n = 5) received obinutuzumab before treatment to study the prevention of antidrug antibodies. The MTD was not determined; 15 mg weekly or 20 mg every 2 weeks of CA plus atezolizumab was the RDE. The safety profile was consistent with CA monotherapy and atezolizumab-based therapies. The addition of atezolizumab did not affect the pharmacokinetic profile of CA, and treatment induced the proliferation of T and NK cells in the blood without Treg expansion. Increases in pharmacodynamic markers (C-reactive protein, lymphocytes, sCD25, and cytokines) suggested immune activation despite limited antitumor activity (overall response rate: 13.5% with weekly/every-3-week regimen).
CONCLUSIONS: The safety profile of this combination was manageable. Prominent pharmacodynamic effects were elucidated; antitumor activity was limited.
PATIENTS AND METHODS: Patients received escalating doses of CA (6-20/25 mg) with fixed dosages of atezolizumab (840 mg) every 2 weeks or escalating dosages of CA weekly (10-15/20 mg) with fixed dosages of atezolizumab (1,200 mg) every 3 weeks. Primary objectives include maximum tolerated dose (MTD), recommended dose for expansion (RDE), and safety.
RESULTS: Twenty-four patients were randomized to receive CA plus atezolizumab every 2 weeks and 45 patients to CA weekly plus atezolizumab every 3 weeks. A subgroup of patients (n = 5) received obinutuzumab before treatment to study the prevention of antidrug antibodies. The MTD was not determined; 15 mg weekly or 20 mg every 2 weeks of CA plus atezolizumab was the RDE. The safety profile was consistent with CA monotherapy and atezolizumab-based therapies. The addition of atezolizumab did not affect the pharmacokinetic profile of CA, and treatment induced the proliferation of T and NK cells in the blood without Treg expansion. Increases in pharmacodynamic markers (C-reactive protein, lymphocytes, sCD25, and cytokines) suggested immune activation despite limited antitumor activity (overall response rate: 13.5% with weekly/every-3-week regimen).
CONCLUSIONS: The safety profile of this combination was manageable. Prominent pharmacodynamic effects were elucidated; antitumor activity was limited.