Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial

Birrer, M; Li, G; Yunokawa, M; Lee, JY; Kim, BG; Oppermann, CP; Zhou, Q; Nishio, S; Okamoto, A; Wu, X; Mileshkin, L; Oaknin, A; Ray-Coquard, I; Hasegawa, K; Jehl, G; Vugmeyster, Y; Zhang, S; Bajars, M; Yonemori, K

Author(s): Birrer, M; Li, G; Yunokawa, M; Lee, JY; Kim, BG; Oppermann, CP; Zhou, Q; Nishio, S; Okamoto, A; Wu, X; Mileshkin, L; Oaknin, A; Ray-Coquard, I; Hasegawa, K; Jehl, G; Vugmeyster, Y; Zhang, S; Bajars, M; Yonemori, K;
Details: Publication Year 2024-09-01,Volume 10,Issue #9,Page 1204-1211
Journal Title: JAMA Oncology
Publication Type: Research article
Abstract: IMPORTANCE: Cervical cancer is a common and lethal cancer worldwide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (or transforming growth factor β trap) fused via a flexible linker to the C-terminus of each heavy chain of an immunoglobulin G1 antibody blocking programmed cell death 1 ligand 1. OBJECTIVE: To evaluate the safety and response rates of bintrafusp alfa in patients with recurrent or metastatic cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 nonrandomized controlled trial evaluated bintrafusp alfa monotherapy in patients with recurrent or metastatic cervical cancer with disease progression during or after platinum-based chemotherapy. Data were collected from March 2020 to February 2022. INTERVENTION: Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee. RESULTS: At data cutoff, 146 of 203 screened patients received 1 or more doses of bintrafusp alfa; of these, the median (range) age was 53 (24-79) years. The study met its primary end point of a 95% CI above the objective response rate benchmark of 15%, with a confirmed objective response rate of 21.9% (95% CI, 15.5-29.5) per the independent review committee. Of these patients, 19 (59.4%) had a durable response of 6 months or more. At data cutoff, responses were ongoing in 13 of 32 responders (40.6%). The most common treatment-related adverse events were anemia (25 [17.1%]), rash (21 [14.4%]), hypothyroidism (15 [10.3%]), and pruritus (15 [10.3%]). Any-cause adverse events of special interest included anemia (82[56.2%]), bleeding events (81 [55.5%]), and immune-related adverse events (49 [33.6%]). CONCLUSIONS AND RELEVANCE: This phase 2 nonrandomized controlled trial of bintrafusp alfa met its primary end point, which may support the potential of a bispecific therapy targeting transforming growth factor β and programmed cell death 1 ligand 1 in patients with recurrent or metastatic cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04246489.
Publisher: JAMA Network
Keywords: Humans; Female; *Uterine Cervical Neoplasms/drug therapy/pathology; Middle Aged; Adult; Aged; *Neoplasm Recurrence, Local/drug therapy; Recombinant Fusion Proteins/therapeutic use/adverse effects; Neoplasm Metastasis
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1001/jamaoncol.2024.2145
Open Access at Publisher's Site: https://doi.org/10.1001/jamaoncol.2024.2145
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-25 07:46:47

Last Modified: 2024-09-25 07:47:07