Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer

Abstract

Balstilimab elicited promising and durable clinical activity in patients with recurrent/metastatic cervical cancer.• Tumor responses occurred irrespective of tumor PD-L1 status or histology.• Balstilimab is well tolerated, with a safety profile consistent with other PD-1 inhibitors.• These findings highlight balstilimab as an attractive candidate for both single-agent and combination-based immunotherapy.

The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways

“…However, limited efficacy in specific histological types of cervical cancer emphasizes the challenges observed previously with anti–PD-(L)1 monotherapies. Similar to balstilimab monotherapy ( 93 ), the combination of balstilimab and zalifrelimab showed lower response rates in patients with cervical adenocarcinoma than those with squamous cell carcinoma (8.8% vs 32.6%) ( 102 ).…”

“…Responses to bintrafusp alfa were long-lasting, with a median DOR of 11.7 months (range, 1.4-41.2 months), and were observed irrespective of tumor histology or prior bevacizumab treatment. In contrast, anti–PD-(L)1 therapies tend to be less effective in patients with adenocarcinoma ( 93 , 102 , 115 ) and those who have been exposed to bevacizumab ( 37 , 102 ). Additionally, the safety profile of bintrafusp alfa in patients with heavily pretreated recurrent or metastatic cervical cancer who had disease progression with platinum-containing chemotherapy was consistent with that of anti–PD-(L)1 therapies, except for treatment-related AEs known to be associated with TGF-β inhibitors (e.g., localized skin lesions including keratoacanthomas) ( 94 , 109 ).…”

“…In the NRG-GY002 trial, nivolumab treatment resulted in one partial response in 15 patients (6.7%) with squamous cell carcinoma, but no responses occurred in the six patients with adenocarcinoma ( 115 ). In a phase 2 study with balstilimab monotherapy in patients with at least one prior chemotherapy, responses were seen in 15 of 85 patients (17.6%) with squamous cell carcinoma and in six of 48 (12.5%) with adenocarcinoma ( 93 ). In the KEYNOTE-158 trial, only one of five patients with adenocarcinoma had a response, making it difficult to draw any conclusions; 11 of 92 patients (12%) with squamous cell carcinoma had a response ( 37 ).…”

Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

“…Overall, pembrolizumab was the most researched agent ( n = 7, [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]), and it is the only agent with published results of a phase III trial [ 17 ]. Other checkpoint inhibitors included nivolumab ( n = 4, [ 24 , 25 , 26 , 27 ]), atezolizumab ( n = 2, [ 28 , 29 ]), ipilimumab ( n = 2, [ 30 , 31 ]), camrelizumab ( n = 1, [ 32 ]), cemiplimab ( n = 1, [ 33 ]), balstilimab ( n = 1, [ 34 ]), bintrafusp alfa ( n = 1, [ 35 ]), navoximod ( n = 1, [ 29 ]) and monolizumab ( n = 1, [ 36 ]), which is an anti-NKG2A (inhibitory receptor on natural killer cells) antibody. A total of 3 trials assessed a combination of immunotherapies from different subgroups (e.g., ICI plus vaccine) and are thus addressed and counted to both subgroups.…”

“…On the contrary, a response rate of 7.9% in PD-L1 negative patients ( n = 38%) was seen under balstilimab monotherapy in patients with metastatic, persistent or recurrent cervical cancer. However, a larger ORR of 20% was seen in PD-L1 positive patients ( n = 58) [ 34 ].…”