Cadonilimab Yields 100% 24-Month OS in Recurrent Cervical Cancer Population

Cadonilimab (AK104), a first-in-class bispecific antibody targeting PD-1 and CTLA-4, demonstrated a 100% 24-month overall survival (OS) rate in those who achieved a complete response (CR) among patients with recurrent or metastatic cervical cancer who progressed on prior platinum-containing chemotherapy in the phase 2 COMPASSION-03 trial (NCT03852251).¹ The updated findings, presented at the 27th European Congress on Gynecological Oncology, highlighted a strong correlation between the depth of tumor response and long-term survival outcomes in patients who had progressed on prior systemic therapies.

Results

The analysis included 99 efficacy-evaluable patients with a median follow-up of 26.5 months. Investigators stratified outcomes based on the best overall response (BOR) to quantify the impact of treatment depth. Among those achieving a CR, both the median OS and median progression-free survival (PFS) were not reached. The 12-month PFS rate for complete responders was 84.6% (P <.0001). As noted previously, the 24-month OS rate was 100.0% (P = .0002).

Patients achieving a partial response (PR) also showed favorable outcomes, with a median OS that was not yet reached and a 24-month OS rate of 63% (P = .0002). The median PFS in this group was 11.17 months, with a 12-month PFS rate of 47.3% (P <.0001).

Notably, the median time to response was similar between the CR and PR cohorts, at 1.84 vs 1.87 months, respectively. The median duration of response (DOR) was not reached in the CR group, and in the PR group, it was “significantly longer than that” (P = .035).¹

Regardless of PD-L1 expression status, cadonilimab monotherapy yielded a median OS of 17.5 months (95% CI, 11.4-not estimable) in the overall population; the 18- and 24-month OS rates were 47.8% and 40.9%, respectively.

Trial Breakdown

Patients in the trial received cadonilimab monotherapy via intravenous administration every 2 weeks.² Those eligible for enrollment in phase 1b cohort 1 had histologically or cytologically documented advanced or metastatic solid tumors that were refractory/relapsed to standard therapies. For other cohorts, patients had gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.

Reportedly, 18% of enrolled patients had a PD-L1 combined positive score of less than 1, and 36% had received at least 2 prior lines of systemic therapy.

Additional enrollment criteria included an ECOG performance status of 0 or 1, an estimated life expectancy of at least 3 months, at least 1 measurable lesion per RECIST v1.1 criteria, and adequate organ function.

Exclusion criteria included receipt of radiotherapy or anti-tumor treatment within 4 weeks of first study dose, prior exposure to any anti–PD-(L)1 or anti–CTLA-4 antibody, history of primary immunodeficiency virus infection, active infection requiring systemic therapy, and central nervous system metastasis.

The primary end point of the trial was the number of patients experiencing adverse events and dose-limiting toxicities.

Next Steps

While the phase 2 results are promising, the single-arm nature of the BOR-stratified analysis limits direct comparisons to current second-line standards. Further validation is underway in the global phase 2 COMPASSION-36 trial, a registrational study evaluating cadonilimab plus lenvatinib (Lenvima) in patients with advanced hepatocellular carcinoma (HCC) previously treated with immunotherapy.³ In August 2025, developers announced that the FDA and China’s National Medical Products Administration approved the initiation of the registrational trial. Investigators aim to address the issue of limited treatment options after resistance to immune checkpoint inhibitors among this HCC population.

Cadonilimab is currently approved in China for first-line gastric cancer, first-line cervical cancer, and recurrent/metastatic cervical cancer.

References

1. Akeso Inc. Cadonilimab achieves 100% 24-month OS in complete responders in hepatocellular carcinoma based on long-term phase II results. News release. Akeso, Inc. March 4, 2026. Accessed March 5, 2026. https://tinyurl.com/2avx9vpv
2. A study of AK104, a PD-1/​CTLA-4 bispecific antibody, for advanced solid tumors or with mXELOX/​XELOX as first-line therapy for advanced gastric or GEJ adenocarcinoma. ClinicalTrials.gov. Updated August 2, 2024. Accessed March 5, 2026. https://tinyurl.com/et4hbh8d
3. Akeso announces approval to initiate global registrational trial of cadonilimab (PD-1/CTLA-4) for PD-1 treatment-resistant hepatocellular carcinoma. News release. Akeso, Inc. August 4, 2025. Accessed March 5, 2026. https://tinyurl.com/yzn6em24