KEYNOTE-032: A Randomized Phase I Study of Pembrolizumab in Chinese Patients with Advanced Non–Small-Cell Lung Cancer
Mené en Chine sur 42 patients atteints d'un cancer du poumon non à petites cellules de stade localement avancé et/ou métastatique, cet essai de phase I analyse les caractéristiques pharmacocinétiques et la toxicité du pembrolizumab, après l'échec de traitements ou une inéligibilité à un traitement standard
Background : The KEYNOTE‐032 study evaluated pembrolizumab pharmacokinetics and clinical outcomes in Chinese patients with locally advanced and/or metastatic non‐small‐cell lung cancer (NSCLC) and prior treatment failure and/or ineligibility for standard therapy. Methods : Patients were randomized 1:1:1 to pembrolizumab 2 mg/kg, 10 mg/kg, or 200 mg every 3 weeks (up to 35 cycles). Safety and pharmacokinetics were primary endpoints; antitumor activity was a secondary endpoint. Results : A total of 42 of 44 randomized patients received pembrolizumab treatment (2 mg/kg, n = 14; 10 mg/kg, n = 13; 200 mg, n = 15). Treatment‐related adverse events (AEs) occurred in 29 of 42 (69%) patients (grade 3–4, 4/42 [10%]); 5 (12%) had immune‐mediated AEs and infusion reactions. Pembrolizumab single dose half‐life following 2 mg/kg, 10 mg/kg, and 200 mg was 15.1, 15.8, and 12.3 days, respectively. Serum exposure at the doses studied (range, 2–10 mg/kg) was approximately linear; steady‐state area under the curve0–21 days (95% confidence interval [CI]) was 730.9 (627.4–851.6), 2,819.2 (2,009.4–3,955.4), and 931.0 (724.4–1,196.6)
μg•day/mL, respectively. After 7.9 (range, 0.7–13.1) months median follow‐up overall, objective response rate was 14.3% (95% CI, 5.4%–28.5%); median progression‐free survival was 2.1 (95% CI, 2.1–4.2) months, and median overall survival was not reached (95% CI, 6.6 months–not reached). Conclusion
:
Pembrolizumab had manageable toxicity, linear serum exposure, and encouraging antitumor activity in Chinese patients with advanced NSCLC.
The Oncologist 2020