Zimberelimab Combo Elicits Activity in Previously Treated Cervical Cancer

“Zimberelimab plus lenvatinib showed promising antitumor activity in patients with advanced cervical cancer who have experienced disease progression after prior ICI therapy,” according to study author Chunyan Lan, MD, PhD.

Treatment with zimberelimab plus lenvatinib (Lenvima) demonstrated promising clinical activity in a small cohort of patients with advanced cervical cancer who experienced disease progression on prior treatment with immune checkpoint inhibitor (ICI) therapy, according to findings from a phase 2 trial (NCT05824468) presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO).¹

Among 30 evaluable patients, study treatment yielded an objective response rate (ORR) of 33.3% (95% CI, 17.3%-52.8%), which consisted entirely of partial responses (PRs). Data also showed a disease control rate (DCR) of 96.7% (95% CI, 82.8%-99.9%).

Across the PD-L1 expression subgroups, there were 4 and 10 patients with and without a response in the PD-L1–positive group, respectively; there were 4 responders and 5 without a response in the PD-L1–negative disease group. Six patients responded and 11 did not respond among those with human papillomavirus (HPV)-16–positive or HPV-18–positive disease, while 3 had a response vs 5 of those who did not in the other high-risk HPV subtype group.

Treatment produced a median progression-free survival (PFS) of 7.1 months (95% CI, 5.1-not reached [NR]). Data did not show a statistically significant correlation between PFS outcomes and PD-L1 expression status (P = .771) or HPV subtypes (P = .614).

“Zimberelimab plus lenvatinib showed promising antitumor activity in patients with advanced cervical cancer who have experienced disease progression after prior ICI therapy,” Chunyan Lan, MD, PhD, of the Department of Gynecologic Oncology at Sun Yat-sen University Cancer Centre in Guangzhou, China; and a member of State Key Laboratory of Oncology in South China of the Collaborative Innovation Centre for Cancer Medicine in Guangzhou, China, stated with study coauthors. “The combination therapy had a favorable and manageable safety profile.”

Investigators conducted this multicenter, single-arm phase 2 trial to assess the efficacy and safety of rechallenging ICI therapy in patients with advanced cervical cancer who previously received ICIs. During the safety run-in portion of the study, patients received lenvatinib at 16 mg once daily plus zimberelimab at 240 mg intravenously every 3 weeks as part of dose level 1 or lenvatinib at 12 mg once daily plus zimberelimab at 240 mg every 3 weeks as part of dose level 2. Following the safety run-in phase, patients were assigned to receive lenvatinib at the recommended phase 2 dose plus the same dose of zimberelimab.

The trial’s primary end point was ORR. Secondary end points included DCR, duration of response, PFS, overall survival, and safety. Investigators assessed potential biomarkers associated with efficacy as an exploratory end point.

Patients 18 to 75 years old with histologically confirmed metastatic, recurrent, or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not amenable to curative therapy with surgery and/or radiation were eligible for enrollment on the study.² Other criteria for study entry included having progression on or after prior ICIs with treatment exposure of more than 6 months, measurable disease per RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, and a life expectancy of more than 3 months.

Patients were enrolled from May 10, 2023, to May 22, 2024. The data cutoff date was July 20, 2024, and the median follow-up was 6.9 months (range, 1.9-14.2). Overall, 30 patients made up the full analysis set and the safety analysis set, while 28 were included in the efficacy evaluable set.

The median patient age was 54 years (range, 32-70). Most of the population had an ECOG performance status of 1 (86.7%), squamous cell carcinoma (63.3%), and 2 prior lines of systemic therapy (43.3%). The most common prior ICIs in this population included tislelizumab (Tevimbra; 36.7%), camrelizumab (Airuika; 16.7%), and sintilimab (Tyvyt; 16.7%). Additionally, most patients received prior radiotherapy (90.0%) and platinum-based treatment (100.0%).

According to the investigators, most treatment-related adverse effects (TRAEs) were mild or moderate in severity. Additionally, 10% (n = 3) of patients experienced grade 3/4 TRAEs, with the most common including proteinuria (3.3%), hand-foot syndrome (3.3%), aspartate aminotransferase increase (3.3%), and alanine aminotransferase increase (3.3%).

References

1. Lan C, Zhang P, Zhao J, et al. Zimberelimab plus lenvatinib in patients with advanced cervical cancer who progressed after prior immune checkpoint inhibitors: a multicenter, single-arm, phase II trial. Presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO); March 14-17, 2025; Seattle, WA.
2. Zimberelimab plus lenvatinib after progression on prior immune checkpoint inhibitors for advanced cervical cancer. ClinicalTrials.gov. Updated April 21, 2023. Accessed March 15, 2025. https://tinyurl.com/2pwxyhc2