Zimberelimab demonstrated encouraging efficacy with a tolerable safety profile in patients with PD-L1–positive recurrent or metastatic cervical cancer who had progressed after first- or subsequent-line, platinum-containing chemotherapy.
Zimberelimab (GLS-010) exhibited promising responses and a manageable safety profile in patients with PD-L1–positive, recurrent or metastatic cervical cancer who had progressed after first- or subsequent-line, platinum-containing chemotherapy, according to findings presented at the 2022 SITC Annual Meeting (NCT03972722).
The phase 2 findings showed that patients treated with the fully human anti–PD-1 monoclonal antibody (n = 90) achieved an overall response rate (ORR) of 27.8% (95% CI, 18.85%-38.22%) per independent review committee (IRC), including a complete response rate of 5.6%, a partial response rate at 22.2%, and a stable disease rate of 26.7%. The disease control rate (DCR) was 54.4% (95% CI, 43.60%-64.98%).
“In this pivotal registration phase 2 study, zimberelimab exhibited encouraging therapeutic activity and a manageable safety profile in [patients with] PD-L1–positive recurrent or metastatic cervical cancer,” lead study author, Xiaohua Wu, MD, of Fudan University Shanghai Cancer Center, in Shanghai, China, and colleagues, wrote in the poster presentation of the data.
Zimberelimab previously displayed acceptable safety and preliminary efficacy in a phase 1 study. The phase 2 trial evaluated the agent in patients with PD-L1–positive, recurrent or metastatic cervical cancer who progressed after first- or subsequent-line platinum-containing chemotherapy. Moreover, patients were required to have an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria, and adequate organ function.
The study used a Simon’s 2-stage design. Stage 1 enrolled 45 patients who received at least 1 prior line of chemotherapy. Investigators initiated stage 2 (N = 105) after at least 3 patients experienced a CR or PR in Stage 1. All patients received 240 mg of intravenous zimberelimab once every 2 weeks. Treatment continued for 24 months or until disease progression or intolerable toxicity.
Fifteen patients in stage 2 were not eligible for efficacy in the full analysis set because they did not receive prior platinum-based chemotherapy. All 105 patients were evaluable for safety.
At the April 29, 2022, data cutoff and at a median follow-up of 16.9 months, 83 patients had discontinued treatment with zimberelimab, and 22 were still on treatment. Reasons for discontinuation included disease progression (n = 56), adverse effects (AEs; 14), investigator’s judgement (n = 5), patient withdrawal (n = 4), death (n = 2), poor compliance (n = 1), or study drug suspension for more than 4 weeks (n = 1).
ORR per IRC assessment served as the primary end point of the trial. Secondary objectives included investigator-assessed ORR, plus DCR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and time to response (TTR).
The median age of patients evaluable for efficacy from stage 2 was 51 years (range, 31- 75). The majority of patients had an ECOG performance status 1 (62.2%), had previous surgery (71.1%), prior radiotherapy (95.6%), and prior chemotherapy (100%). Moreover, 57.8% of patients received 1 prior line of chemotherapy, 32.2% had previously received 2 lines of chemotherapy, and 10.0% of patients were given at least 3 prior lines of chemotherapy.
Most patients presented with squamous carcinoma (87.8%). Other histologies included adenomatous carcinoma (10%) and adenosquamous carcinoma (2.2%). Finally, 18.9% of patients had stage IB disease, 21.1% had stage IIA, 23.3% had stage IIB, 2.2% had stage IIIA, 11.1% had stage IIIB, 12.2% had stage IIIC, and 7.8% had stage IV.
Additional data showed the median PFS was 3.7 months (95% CI, 1.94-5.55) and the median OS was 16.8 months (95% CI, 11.50–not estimable). The median TTR was 1.9 months (95% CI, 1.84-3.65). The median DOR was not reached, and the 12-month DOR rate was 78% (95% CI, 55%-90%).
Any-grade treatment-emergent AEs (TEAEs) occurred in 97.1% of patients, including grade 3 or higher TEAEs in 41.9% of patients. Any-grade treatment-related AEs (TRAEs) were reported in 78.1% of patients, and 24.8% of patients experienced at least 1 TRAE of grade 3 or higher. Any-grade Immune-related AEs (irAEs) and grade 3 or higher irAEs were reported in 45.7% and 10.5% of patients, respectively. The rates serious AEs and treatment-related serious AEs were 28.6% and 15.2%, respectively.
The most common TRAEs of any grade were hypothyroidism (26.7%), anemia (19.0%), hyperthyroidism (12.4%), elevated aspartate aminotransferase (10.5%), elevated alanine aminotransferase (10.5%), and decreased white blood cell count (10.5%). Grade 3 or higher TRAEs included anemia (7.6%) and decreased white blood cell count (0.7%).
“The trial is still ongoing, and we are looking forward to further results,” Wu and study authors concluded.
Wu X, Xia L G, Wang C, et al. Efficacy and safety of zimberelimab (GLS-010) monotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II study. Presented at: 2022 SITC Annual Meeting; November 8-12, 2022; Boston, MA. Abstract 673.