Neoadjuvant cadonilimab (anti-PD-1/CTLA-4 bispecific antibody) plus chemotherapy in early or locally advanced triple-negative breast cancer: A single-arm phase II trial (CABIN study).

599 Background: Neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) can improve surgical outcomes; however, many patients fail to achieve pathological complete response (pCR). Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 show promise, but responses are limited. This phase II trial evaluates cadonilimab (AK104), a bispecific PD-1/CTLA-4 antibody, combined with nab-paclitaxel and carboplatin in neoadjuvant TNBC to improve pCR rates and assess safety. Methods: This phase II, single-arm trial enrolled patients aged 18-75 with treatment-naïve, stage IA-IIIC triple-negative breast cancer (TNBC). Patients received cadonilimab (10 mg/kg) plus nab-paclitaxel (260 mg/m²) and carboplatin (AUC 4) every 3 weeks for six cycles, followed by surgery within 4 weeks. Biopsy specimens were collected before treatment for whole-exome sequencing. The primary endpoint was total pathological complete response (tpCR) rate (ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and safety. Results: A total of 29 patients were enrolled from January 31, 2023, to January 20, 2025. The median age was 53 years, and 11 patients (37.9%) were premenopausal. The majority had positive nodal involvement (75.9%) and stage III (51.7%) disease. of the 29 patients, 19 (65.5%, 95% CI: 45.7-82.1) achieved total pathological complete response (tpCR), and 21 (72.4%, 95% CI: 52.8-87.3) achieved breast pCR (bpCR). Tumor downstaging occurred in 89.7% (T) and 62.1% (N) of patients. Radiological assessments showed an objective response rate (ORR) of 93.1% (95% CI: 77.2-99.2) and a disease control rate (DCR) of 100%. All patients experienced at least one treatment-related adverse event (TRAEs), with 51.7% having grade 3/4 events, most commonly neutropenia (37.9%), platelet count decrease (19.2%), and leukopenia (17.2%). Serious TRAEs occurred in 6.9%. Immune-related adverse events (irAEs) of any grade occurred in 14 (48.0%) patients, while those of grade ≥ 3 occurred in only one patient (3.4%). The most common irAE was hypothyroidism (44.8%, 13/29), all were grade 1 or 2. Notably, patients with TASOR2 or MST1R mutation demonstrated a significantly lower pCR rate (both P =0.041). Additionally, CCND1 amplification showed a non-significant negative trend with the pCR rate ( P =0.051). Conclusions: The combination of cadonilimab, nab-paclitaxel, and carboplatin in neoadjuvant treatment for stage IA-IIIC TNBC showed promising efficacy, with high response rates and significant tumor downstaging, particularly in stage III patients. The regimen was well tolerated with manageable adverse events, supporting its further investigation as a potential neoadjuvant treatment for TNBC. Clinical trial information: ChiCTR2200067005 .