Incyte starts pivotal Dawn-03 trial of INCB161734 in KRAS G12D-mutant pancreatic cancer
Incyte has started the phase 3 Dawn-03 trial of INCB161734 plus chemotherapy in first-line KRAS G12D-mutant pancreatic cancer. The move comes while the phase 1 study remains halted in four European countries after pneumonitis cases, including one grade 5 event.
Incyte has started the pivotal Dawn-03 trial of INCB161734 in combination with chemotherapy versus chemotherapy alone as a first-line treatment for patients with KRAS G12D-mutant pancreatic cancer. The phase 3 study is recruiting, and its primary endpoints are overall survival, progression-free survival and overall response rate. The trial has a primary completion date of September 2028.
The move takes INCB161734 from phase 1 into pivotal development even though the phase 1 study remains halted in Spain, Italy, Belgium and France since February 2026 owing to pneumonitis. The clinical hold was triggered by a case of grade 5 pneumonitis in a patient.
After the fatality, the company reviewed the approximately 300 other enrolled patients and identified three additional cases of confirmed or suspected pneumonitis, all linked to the 1.2g dose. Three of the four cases occurred in cohorts receiving the combination with chemotherapy, the same regimen now under investigation in the Dawn-03 trial.
The new registry entry does not specify the dose that will be used in the pivotal study. The phase 1 study enrolled patients with a diverse range of solid tumours, including pancreatic ductal adenocarcinoma, colorectal cancer, non-small cell lung cancer and ovarian cancer.
A separate first-in-human trial of INCB186748, an apparent follow-up KRAS G12D asset, is marked as active, not recruiting, with 30 subjects enrolled versus an initial recruitment target of 308 patients.