In the phase 1b/2 TRIFOUR trial, adding the anti-IL1RAP antibody nadunolimab (CAN04) to gemcitabine/carboplatin chemotherapy produced comparable overall survival to chemotherapy alone in metastatic triple-negative breast cancer (TNBC), but did not demonstrate a clinically meaningful efficacy benefit.
Newly reported overall survival data, a secondary endpoint, showed identical median OS of 26 months for both the nadunolimab plus GC arm and the GC-alone arm, substantially exceeding historical medians of about 11 to 13 months for this aggressive subtype.
Topline results reported earlier also found no meaningful difference in the primary endpoint of overall response rate, with ORRs of 40% versus 43% for the investigational and comparator arms. Both response rates surpassed historically reported figures of roughly 30% for GC in first- and second-line TNBC.
The safety profile remained consistent with prior nadunolimab data. Neutropenia and asthenia were the most common adverse events, and no significant safety differences emerged between the two treatment groups.
Cantargia has decided to halt development of nadunolimab in TNBC due to the lack of meaningful efficacy signals, although patients already benefiting in TRIFOUR will continue treatment. Final TRIFOUR data will be presented at an upcoming medical conference. “We view this outcome in TNBC as indication specific, not predictive and not translating to pancreatic or lung cancer, where the biology, standard of care, and heterogeneity of the TRIFOUR patient population differ significantly,” said Wolfram Dempke, MD, PhD, MBA, Cantargia’s chief medical officer.
TRIFOUR is an open-label study run in Spain by the Spanish Breast Cancer Group. In the randomized phase 2 portion, 99 patients with metastatic TNBC eligible for first- or second-line GC were randomized to nadunolimab plus GC (n = 51) or GC alone (n = 48). Investigational-arm patients received 2.5 mg/kg nadunolimab twice per 3- to 4-week cycle after initial step-up dosing, alongside intravenous gemcitabine and carboplatin.
Despite the TNBC outcome, nadunolimab continues to show potential in other indications. The antibody has received FDA Fast Track designation for metastatic pancreatic ductal adenocarcinoma (PDAC) with high IL1RAP expression.
In the phase 2 CANFOUR trial in PDAC, nadunolimab with gemcitabine and nab‑paclitaxel produced a median OS of 13.2 months and a 1-year survival rate of 58%, with a manageable safety profile. CANFOUR also included 40 patients with advanced or metastatic non–small cell lung cancer; published data reported a median OS of 13.7 months, 54% 1-year survival, and notable benefit among patients previously treated with pembrolizumab.
“While the combined results, including the primary end point and subgroup analyses, indicate that the TRIFOUR study did not meet its objectives, we recognize the valuable insights gained from this trial,” said Cantargia CEO Hilde Steineger. She added that the company remains confident in nadunolimab’s potential, particularly in PDAC, where ongoing data and scientific rationale support further development.
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