PT  - JOURNAL ARTICLE
AU  - Strauss, J
AU  - Braiteh, F
AU  - Calvo Aller, E
AU  - De Miguel, M
AU  - Cervantes, A
AU  - Edenfield, WJ
AU  - LI, T
AU  - Rasschaert, MA
AU  - Park-Simon, TW
AU  - Munoz, FL
AU  - Paz-Ares, L
AU  - Spira, A
AU  - Jehl, G
AU  - Dussault, I
AU  - Ojalvo, L
AU  - Gulley, J
AU  - Allan, S
TI  - 116 Evaluation of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer: data from phase 1 and phase 2 studies
AID  - 10.1136/ijgc-2021-ESGO.8
DP  - 2021 Oct 01
TA  - International Journal of Gynecologic Cancer
PG  - A5--A6
VI  - 31
IP  - Suppl 3
4099  - http://ijgc.bmj.com/content/31/Suppl_3/A5.short
4100  - http://ijgc.bmj.com/content/31/Suppl_3/A5.full
SO  - Int J Gynecol Cancer2021 Oct 01; 31
AB  - Introduction/Background*The accelerated US Food and Drug Administration approval of pembrolizumab validated the efficacy of anti-PD-(L)1 therapy for patients with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in patients with PD-L1–expressing tumours. Human papillomavirus infection is implicated in >95% of cervical cancers and is linked to upregulation of TGF-β signalling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 monoclonal antibody blocking PD-L1. We report pooled safety and efficacy in patients with pretreated, immune checkpoint inhibitor-naive, recurrent/metastatic cervical cancer treated with bintrafusp alfa in phase 1 (INTR@PID 001; NCT02517398) and phase 2 (study 012; NCT03427411) studies.Methodology Patients received bintrafusp alfa 0.3-30 mg/kg (phase 1 dose escalation) or 1200 mg every 2 weeks (phase 1 dose expansion and phase 2) until progressive disease, unacceptable toxicity, or withdrawal. Treatment past progression was allowed. Primary endpoints were safety (phase 1 dose escalation) and best overall response per RECIST 1.1 (phase 1 dose expansion and phase 2).Result(s)*As of May 15, 2020 (phase 1) and December 22, 2020 (phase 2), 39 patients had received bintrafusp alfa for a median duration of 2.8 months (range, 0.5-19.3). The median follow-up to data cutoff was 35.0 months and 24.1 months for the phase 1 and phase 2 studies, respectively. All patients had received prior anticancer therapy; 16 (41.0%) had received ≥3 regimens. Confirmed ORR was 28.2% (table 1); responses occurred irrespective of Moore criteria (phase 1), tumour histology, prior bevacizumab treatment, or radiation treatment. Median overall survival was 13.4 months. No new safety signals and no treatment-related deaths were observed; side effects were manageable.View this table:Abstract 116 Table 1 Conclusion*Bintrafusp alfa had a manageable safety profile and demonstrated clinical activity in patients with heavily pretreated, immune checkpoint inhibitor-naive recurrent/metastatic cervical cancer.© 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.