Adding the anti-IL1RAP antibody nadunolimab (CAN04) to gemcitabine/carboplatin (GC) produced comparable overall survival (OS) to GC alone in the phase 1b/2 TRIFOUR trial (NCT05181462) for metastatic triple-negative breast cancer (TNBC), but did not demonstrate a clinically meaningful efficacy benefit, Cantargia reported.
Newly released OS data, a secondary endpoint, showed a median OS of 26 months in both the nadunolimab-plus-GC and GC-alone arms, substantially longer than historical expectations for this aggressive subtype, where median OS typically ranges from about 11 to 13 months.
Topline results reported earlier also found no meaningful difference in the trial’s primary endpoint of overall response rate (ORR), with ORRs of 40% for the combination and 43% for GC alone. Both response rates exceeded historical figures of roughly 30% for GC in first- and second-line TNBC settings.
Safety findings remained consistent with prior nadunolimab data. Neutropenia and asthenia were the most common adverse events, and no significant safety differences were observed between the two treatment groups.
Cantargia said it will stop development of nadunolimab in TNBC due to the lack of meaningful efficacy signals, though patients already benefiting from treatment in TRIFOUR will continue on study and final trial 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, chief medical officer at Cantargia.
The open-label TRIFOUR trial, run in Spain by the Spanish Breast Cancer Group, randomized 99 patients with metastatic TNBC eligible for first- or second-line GC 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 intravenous gemcitabine and carboplatin.
Cantargia said nadunolimab will continue development in other indications. The antibody has received FDA Fast Track designation for metastatic pancreatic ductal adenocarcinoma (PDAC) with high IL1RAP expression. In the CANFOUR trial (NCT03267316), nadunolimab with gemcitabine/nab-paclitaxel achieved a median OS of 13.2 months and a 1-year survival rate of 58% in locally advanced or metastatic PDAC. Early data in non–small cell lung cancer showed a median OS of 13.7 months and a 1-year survival rate of 54%, with notable benefit in patients previously treated with pembrolizumab.
“Although this is not the outcome we had hoped for, we remain confident in the strong potential of nadunolimab, particularly in PDAC, where we see strong scientific rationale, robust data and significant opportunities for impact,” said Hilde Steineger, CEO of Cantargia.
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