TY - JOUR
T1 - Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer
AU - Oaknin, Ana
AU - Ghamande, Sharad A.
AU - Kasamatsu, Yuka
AU - Gil-Martin, Marta
AU - Grau-Bejar, Juan Francisco
AU - Garcia-Duran, Carmen
AU - Sato, Masashi
AU - Siddiqui, Abdul
AU - Chaudhary, Surendra Pal
AU - Vugmeyster, Yulia
AU - Hasegawa, Kosei
N1 - Publisher Copyright:
©2024 The Authors; Published by the American Association for Cancer Research.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Purpose: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFb receptor II (a TGFb “trap”) fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer. Patients and Methods: In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n ¼ 8) or without (Cohort 1B; n ¼ 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n ¼ 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics. Results: At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1–2 in severity, most commonly anemia (62.5%–77.8%) and bleeding events (62.5%–77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9–96.8], 44.4% (95% CI, 13.7–78.8), and 62.5% (95% CI, 24.5–91.5) in Cohorts 1A, 1B, and 2, respectively. Conclusions: Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFb/PD-L1 inhibition in human papillomavirus–associated cancers, including cervical cancer.
AB - Purpose: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFb receptor II (a TGFb “trap”) fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer. Patients and Methods: In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n ¼ 8) or without (Cohort 1B; n ¼ 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n ¼ 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics. Results: At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1–2 in severity, most commonly anemia (62.5%–77.8%) and bleeding events (62.5%–77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9–96.8], 44.4% (95% CI, 13.7–78.8), and 62.5% (95% CI, 24.5–91.5) in Cohorts 1A, 1B, and 2, respectively. Conclusions: Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFb/PD-L1 inhibition in human papillomavirus–associated cancers, including cervical cancer.
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U2 - 10.1158/1078-0432.CCR-23-1829
DO - 10.1158/1078-0432.CCR-23-1829
M3 - Article
C2 - 38165683
AN - SCOPUS:85186745319
SN - 1078-0432
VL - 30
SP - 975
EP - 983
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -