Precemtabart tocentecan (Precem-TcT, M9140), an anti-CEACAM5 antibody-drug conjugate (ADC), in patients with metastatic pancreatic ductal carcinoma (mPDAC): Results from the phase 1b/2 PROCEADE-PanTumor PDAC substudy.

4199 Background: CEACAM5 is overexpressed in many cancers, including PDAC, with limited expression in normal tissues. Precem-TcT, an anti-CEACAM5 ADC with an exatecan payload (topoisomerase 1 inhibitor TOP1i), showed a predictable, manageable safety profile and promising clinical activity (ORR: 31.0%; mPFS: 6.9 months) in the Phase 1 PROCEADE-CRC-01 study (NCT05464030) in patients with heavily pretreated metastatic colorectal cancer (mCRC). Methods: PROCEADE-PanTumor (NCT06710132) is an ongoing, Phase 1b/2, open-label study investigating the efficacy and safety of Precem-TcT monotherapy in advanced PDAC, gastric cancer, and non-small cell lung cancer. Here, we report interim results from the PDAC substudy, which enrolled patients with pretreated mPDAC (ECOG PS ≤1; and CEACAM5 high expression ≥50% tumor cells with immunohistochemistry ≥2+ staining) in the US, Australia, France, Japan, and Korea, who were treated with Precem-TcT 2.8 mg/kg Q3W. Results: Between May and September 2025, 46 patients have been enrolled into the study (median age: 62.0 years; female: 65.2%; ECOG PS 0/1: 47.8%/52.2%). Most patients received one or two prior lines of therapy, and were irinotecan pretreated. As of November 2025, median duration of Precem-TcT treatment was 12.6 weeks. Treatment emergent adverse events (TEAEs) occurred in 95.7% of patients; grade ≥3: 78.3%. Most common grade ≥3 TEAEs were neutropenia (43.5%) and anemia (32.6%). Gastrointestinal TEAEs were mostly grade 1-2, and there were no cases of interstitial lung disease or ocular toxicities. TEAEs led to dose reductions in 15.2% and to permanent discontinuation in 4.3% of patients. There were no treatment-related deaths. As of January 2026, 10 patients had a PR (21.7%), 20 SD (43.5%), and 11 PD (23.9%); 14 patients remain on study. Updated data, including mPFS and CEACAM5 expression, will be presented at the congress. Preliminary pharmacokinetics of the conjugated antibody and unconjugated exatecan appeared generally consistent with previous data from patients with mCRC. Conclusions: Precem-TcT, the first anti-CEACAM5 ADC with a TOP1i-payload reporting clinical data in patients with mPDAC, showed a predictable safety profile in this population, consistent with data from patients with mCRC. Efficacy data in this highly refractory, mostly irinotecan-pretreated 2L/3L population benchmark favorably with the current SoC for 2L mPDAC. Clinical trial information: NCT06710132 .