Clinical Trial Results

NCT05063916, conducted by MD Anderson Cancer Center, was a single-arm, open-label Phase 2 trial evaluating cadonilimab (AK104, Kaitanni) in patients with recurrent/metastatic cervical small cell neuroendocrine carcinoma. Cadonilimab is a dual-specific antibody that simultaneously blocks PD-1 and CTLA-4, administered at 6 mg/kg every two weeks for up to 24 months. Nine patients were enrolled, with eight included in the efficacy evaluation. The final results were published in the International Journal of Gynecologic Cancers in July 2026. While the study holds academic value as prospective data on a rare cancer, the lack of efficacy signals does not support further development.

Efficacy and Safety

The six-month progression-free survival (PFS) rate was 12.5%, with only one of the eight patients surviving without progression at the six-month mark. The objective response rate (ORR) was 0%, the median PFS (mPFS) was 2.19 months, and the disease control rate (DCR) was 25%, with the duration of the two stable disease lesions being 9.4 weeks and 16.2 weeks, respectively. One of the nine patients experienced Grade 3 fatigue, but there were no Grade 4 or 5 adverse events, indicating that antitumor activity, rather than safety, was the primary limitation. Even considering the study's design as a small, single-arm study, the complete absence of objective response raises concerns about the priority of further development of cadonilimab as a monotherapy.

Competitive Landscape and Standard of Care

This cancer type accounts for approximately 1-1.5% of all cervical cancers, and cisplatin/etoposide combination therapy, based on experience in treating small cell lung cancer, is commonly used. In recurrent settings, a combination of topotecan, paclitaxel, and bevacizumab (VEGF-A inhibitor) has demonstrated an mPFS of 8.7 months compared to 3.7 months with other chemotherapy regimens. A Phase 2 trial of pembrolizumab (Keytruda, PD-1 inhibitor) as a monotherapy also showed limited activity in lower genital tract neuroendocrine carcinomas, highlighting the common limitations of immune checkpoint inhibitor monotherapy. In general recurrent cervical cancer, Keytruda combination therapy and tisotumab vedotin (Tivdak, tissue factor-targeted antibody-drug conjugate) are competitive, but direct evidence for rare neuroendocrine subtypes requires separate validation, as demonstrated in this trial.

Corporate, Regulatory, and Market Implications

Akeso (9926.HK), the developer of cadonilimab, received approval in China on June 29, 2022, for its use as a treatment for recurrent/metastatic cervical cancer after platinum-based chemotherapy. In the United States, Merck's (MRK) Keytruda was approved on October 13, 2021, for use in combination with chemotherapy for persistent/recurrent/metastatic cervical cancer with PD-L1 CPS ≥ 1, and Pfizer's (PFE) Tivdak, acquired through the acquisition of Seagen, received full approval on April 29, 2024, for use in patients who have progressed after chemotherapy. The global cervical cancer treatment market is projected to grow from USD 8.2 billion in 2023 to USD 9.5 billion in 2026 and USD 11.7 billion in 2030, but the neuroendocrine subtype has a very small patient population. Therefore, these results demonstrate that the approved efficacy in general cervical cancer cannot be extended to rare subtypes, and commercial opportunities are limited without combination therapy or biomarker-driven strategies.