David M. O’Malley, MD, Department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC "“ James speaks about the ESMO 2021 Abstract – LBA34 – Single-agent anti-PD-1 balstilimab or in combination with anti-CTLA-4 zalifrelimab for recurrent/metastatic (R/M) cervical cancer (CC): Preliminary results of two independent phase II trials.
Background:
The lack of second-line therapy for R/M CC remains a significant therapeutic need. In R/M CC, data from two phase 2 trials of balstilimab (bal) alone and in conjunction with zalifrelimab (zal) are presented.
Methods:
Patients received bal 3mg/kg q2w (NCT03104699) or bal 1mg/kg q6w (NCT03495882) as a single agent or in combination with zal 1mg/kg q6w for up to 2 years. The primary goal was objective response rates (ORR) as determined by independent review according to RECIST 1.1, with safety and DOR as secondary objectives.
Results:
In the bal and bal/zal, we treated 161 and 155 patients, respectively, with 160 and 143 patients having baseline quantifiable illness (modified ITT population). As per protocol, all pts had previously had platinum-based therapy for their first line. Squamous-cell carcinoma (SCC) was the most common histologic subtype (63 percent bal; 74 percent bal/zal), with adenocarcinoma/adenosquamous/other (AC) being prevalent. CPS 1% (62 percent bal; 55 percent bal/zal) was considered positive, whereas CPS 1% (26 percent bal; 25 percent bal/zal) was considered negative, and unknown (12 percent bal; 20 percent bal/zal) was considered unknown. The data on efficacy may be seen below.
In both studies, the treatment was well tolerated. Immune-related AEs occurred in 49 (30%) of patients in the bal trial and 50 (35%) in the bal/zal study (all grades), with severe (Grade 3+) AEs occurring in 13 (8.0%) and 15 (10.5%) of patients, respectively. Treatment discontinuation was seen in 22 points (13.7%) in bal and 15 points (10%) in bal/zal. The bal study had no treatment-related fatalities, whereas the bal/zal trial had two (nephritis; pneumonitis). There were no new safety signals discovered.
Conclusions:
Both single-agent bal and bal/zal are active and well-tolerated in R/M CC, according to these findings. Adding bal to zal enhanced ORR and DOR while increasing AEs only a little. Responses were more prevalent in PD-L1 + and SCC participants, although they were also evident in PD-L1- and AC participants. This is by far the greatest trial using checkpoint inhibitors in cervical cancer that has been published to date.
Clinical trial identification
NCT03104699, NCT03495882.