Geptanolimab Elicits Durable Responses and Acceptable Safety in PD-L1+ Cervical Cancer

The novel anti-PD-1 antibody geptanolimab (GB226) demonstrated durable antitumor activity and favorable tolerability in patients with recurrent or metastatic PD-L1–positive cervical cancer who previously progressed on a platinum-based regimen, according to initial findings from part 2 of the phase 2 Gxplore-008 trial (NCT03808857).¹

Findings presented at the 2023 ASCO Annual Meeting showed that patients treated with geptanolimab (n = 100) experienced an overall response rate (ORR) of 18% (95% CI, 11.03%-26.95%) according to independent central review (IRC) assessment and RECIST v1.1 criteria. This consisted of 5 complete responses and 13 partial responses (PRs). Stable disease was achieved by 23% of patients, and 51% experienced disease progression; 8% of patients could not be assessed. The disease control rate was 41% (95% CI, 31.26%-51.29%).

Moreover, the median duration of response (DOR) was not yet reached (NR) with the agent (95% CI, 7.16-NR). All patients had an estimated DOR rate of 3 months or greater; 80% of patients had an estimated DOR rate of at least 6 months, and 54% had an estimated DOR rate of 9 months or longer.

“Clinical benefit was observed across most patient subgroups, with a trend of higher ORR in patients with squamous cell carcinoma, no previous bevacizumab [Avastin] use, and high combined positive score,” lead study author Jusheng An, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Chinese Academy of Medical Sciences in Beijing, China, and colleagues, wrote in a poster of the data.

The 2-part, multicenter, single-arm study enrolled patients aged 18 years or older with recurrent or metastatic cervical cancer who had been previously treated with 1 or more lines of platinum-based chemotherapy. Patients were also required to have 1 or more measurable target lesion according to RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and an expected survival of 3 months or more.² Patients were recruited across 28 clinical sites in China.

In part 2 of the trial, patients were intravenously administered a 3-mg/kg dose of geptanolimab once every 2 weeks. Treatment continued until disease progression or death. The primary end point was ORR assessed by IRC.¹ Key secondary end points included DOR, progression-free survival (PFS), overall survival (OS), and safety.

A total of 123 patients were enrolled onto part B of the study. As of the data cutoff date of July 28, 2022, a total of 100 patients met study population criteria after a median follow-up of 16.69 months and were included in the full analysis.

The median age of patients was 51.3 years (range, 26-71), and all were female. Ninety percent of patients had squamous cell carcinoma, and 94% had metastatic disease. The majority had de novo metastatic disease (70%), followed by recurrent metastatic disease (24%) and locally recurrent, inoperable disease (6%). The most common site of metastatic disease was the lymph nodes (65%). An ECOG performance status of 0 and 1 was observed in 22% and 78% of patients, respectively.

Regarding prior therapy, 46% of patients had previously been treated with 2 or more lines of systemic therapy and 93% had received prior radiotherapy. Previous systemic platinum-based therapy and taxanes were received by 99% of patients, 30% of patients had prior exposure to bevacizumab (Avastin).

Previously reported data from part 1 of the study indicated that geptanolimab induced early activity in patients who had PD-L1–positive disease (n = 46), with 11 PRs reported.

Additional data from part 2 showed that treatment with the agent resulted in a median progression-free survival of 1.91 months (95% CI, 1.87-3.55) and a median overall survival (OS) of 16.69 months (95% CI, 11.07-NR).

Safety analysis revealed that geptanolimab had primarily low-grade treatment-related adverse effects (TRAEs). In the 123 safety-evaluable patients, 78.9% experienced a TRAE. Common TRAEs observed in 10% of patients or more included hypothyroidism (any-grade, 24.4%; grade 3, 0.8%), anemia (21.2%; 8.9%), and hyperthyroidism (13.8%; 0%). Grade 3 and 4 TRAEs were observed in 20.3% and 1.6% of patients, respectively. No grade 5 TRAEs occurred.

Serious any-grade TRAEs were experienced by 13% of patients; these effects were grade 3 or 4 in 8.1% and 1.6% of patients, respectively. Common immune-related AEs included hypothyroidism (22%; 0.8%) and hyperthyroidism (13%; 0%). Any-grade infusion reactions were seen in 7.3% of patients.

Any-grade TRAEs led to treatment discontinuation or interruption in 5.7% and 13.8% of patients, respectively.

Editor’s Note: Dr An had no relationships to disclose.

References

1. An J, Zhang Y, Feng M, et al. A multicenter, open-label, single-arm, phase II trial to evaluate the efficacy and safety of geptanolimab (GB226) in the treatment of patients (pts) with programmed cell death ligand 1 (PD-L1)–positive recurrent or metastatic cervical cancer, for whom prior platinum-containing chemotherapy has failed. J Clin Oncol. 2023;41(suppl 16):5535. doi:10.1200/JCO.2023.41.16_suppl.5535
2. A study in recurrent or metastatic cervical cancer patients with PD-L1 positive. ClinicalTrials.gov. Updated March 3, 2021. Accessed August 28, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03808857