Nadunolimab Misses Efficacy Mark in TNBC, Despite Strong OS

Adding the anti-IL1RAP antibody nadunolimab (CAN04) to gemcitabine/carboplatin chemotherapy produced no overall survival benefit versus chemotherapy alone in the phase 1b/2 TRIFOUR trial in metastatic triple-negative breast cancer (TNBC), Cantargia reported. Median overall survival was 26 months in both arms, well above historical expectations for this disease but not different between groups.

The trial’s primary end point, overall response rate, showed no clinically meaningful difference (40% with nadunolimab plus GC versus 43% with GC alone). Both response rates exceeded historical figures of about 30% for GC in first- and second-line TNBC. Safety findings were consistent with prior data on nadunolimab, with neutropenia and asthenia the most common adverse events and no notable safety differences between arms.

TRIFOUR is an open-label study conducted in Spain by the Spanish Breast Cancer Group. In the randomized phase 2 portion, 99 patients eligible for first- or second-line GC were assigned to nadunolimab plus GC (n = 51) or GC alone (n = 48). Patients in the investigational arm received 2.5 mg/kg nadunolimab twice per 3- to 4-week cycle after initial step-up dosing alongside IV chemotherapy.

Because the trial did not show meaningful efficacy signals in TNBC, Cantargia will cease development of nadunolimab in this indication, although treatment within TRIFOUR will continue for patients still deriving benefit and final results will be presented at a medical conference. Cantargia executives described the outcome as indication specific and said it should not be extrapolated to pancreatic or lung cancer, where disease biology and prior data differ.

Nadunolimab remains under development in other cancers. The antibody received FDA Fast Track designation in metastatic pancreatic ductal adenocarcinoma with high IL1RAP expression. In the CANFOUR trial, nadunolimab plus gemcitabine/nab-paclitaxel produced a median overall survival of 13.2 months and a 1-year survival rate of 58% in advanced or metastatic pancreatic cancer. Early data in non–small cell lung cancer also showed encouraging survival outcomes and apparent benefit in patients previously treated with pembrolizumab. Cantargia said it remains confident in nadunolimab’s potential, particularly in pancreatic cancer.