Precemtabart tocentecan (Precem-TcT, M9140) in patients with mCRC: Efficacy and safety data at the recommended development dose in the PROCEADE-CRC-01 study.

129 Background: Precem-TcT, an anti-CEACAM5 ADC with TOP1i payload (exatecan), has shown promising monotherapy efficacy during dose escalation, with a predictable and manageable safety profile in the PROCEADE-CRC-01 study (NCT05464030), in heavily pretreated patients with mCRC who had previously received irinotecan. Methods: Pooled data from the PROCEADE-CRC-01 study were analyzed to evaluate efficacy and safety in all 41 patients treated with Precem-TcT at the recommended development dose of 2.8 mg/kg Q3W (dose escalation, n=12; dose optimization, n=29; data cutoff: 28 May 2025). Patient-reported symptomatic AEs (PRO-CTCAE) were evaluated in the dose optimization (n=29; data cutoff: 07 Jan 2025). Results: Among 41 patients evaluated at 2.8 mg/kg Q3W, all were irinotecan pre-treated and received ≥2L of prior therapy; 24.4% received ≥3L. The objective response rate was 26.8% (95% CI: 14.2, 42.9; n=11), with confirmed responses in 5 patients at data cutoff. Of these 5 patients, 3 had a duration of response of at least 6 months and are ongoing treatment. The median duration of treatment was 6.5 months (min, max: 0.4, 18.6). The median progression-free survival was 6.9 months (95% CI: 4.4, 9.7). The overall safety profile was consistent with that reported for 2.8 mg/kg Q3W at earlier data cutoffs, with no new or unexpected treatment-emergent adverse events (TEAEs). Grade ≥3 TEAEs were primarily hematologic (n=27; 65.9%), with neutropenia (n=20; 48.8%) and anemia (n=18; 43.9%) being the most common. GI toxicities were mostly grade 1/2. Serious treatment-related TEAEs were reported in 6 (14.6%) patients, including 1 treatment-related death due to sepsis (also deemed disease-related; patient had multiple comorbidities). No ILDs or ocular toxicities were reported. TEAEs reported in ≥10% of patients were most frequent during early cycles and did not show a trend for increase or late-onset over the ~9-months observation period. TEAEs led to dose reductions, interruptions/delays, and discontinuations in 12 (29.3%), 23 (56.1%), and 2 (4.9%) patients, respectively. The frequency and severity rates of PRO-CTCAEs for targeted symptomatic AEs in the study were generally in line with the frequency and severity of the reported TEAE rates. Conclusions: Precem-TcT 2.8 mg/kg Q3W (recommended dose for further clinical development) showed clinically meaningful responses in an irinotecan pre-treated mCRC patient population, with a median PFS of 6.9 months that compared favorably with available therapies in the 3L+ setting. TEAEs were mainly hematologic; there were no signs of ILD; rates of GI toxicity were low. OS data will be presented at the congress. Clinical trial information: NCT05464030 .