These findings demonstrate how early-phase data can inform optimal dose selection by quantifying benefit-risk. This robust framework and methodology is generalizable beyond Tusa, offering value to support dose selection and trial decision-making in oncology drug development.

We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials...There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival. Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort.

P1, N=12, Active, not recruiting, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Recruiting --> Active, not recruiting | N=24 --> 12

P1, N=914, Recruiting, Seagen, a wholly owned subsidiary of Pfizer | N=494 --> 914

In CEACAM5 HE, the ORR was greater with high versus low cCEA. Associations were observed between cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; IHC CEACAM5 and CEACAM5 mRNA, but not between IHC CEACAM5 and oncogenic drivers.

P2, N=50, Terminated, Sanofi | Completed --> Terminated; Sponsor decision, the decision is not related to any safety concern.

Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications. Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.

P1, N=494, Recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: May 2030 --> Sep 2030

P3, N=389, Active, not recruiting, Sanofi | Trial completion date: Jun 2025 --> Mar 2026

Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody-drug conjugate with the topoisomerase 1 inhibitor exatecan as payload...In the dose-escalation stage of the phase 1 trial of Precem-TcT (PROCEADE-CRC-01), 40 heavily pretreated patients with irinotecan-refractory metastatic CRC received Precem-TcT every 3 weeks across seven dose levels (DLs, 0.6-3.2 mg kg-1)...The dose-optimization part at the RDEs of 2.4 mg kg-1 and 2.8 mg kg-1 (both every 3 weeks) in PROCEADE-CRC-01 is ongoing. ClinicalTrials.gov identifier: NCT05464030 .

P1, N=200, Recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Feb 2026 --> Aug 2026 | Trial primary completion date: Feb 2026 --> Aug 2026

Tusamitamab ravtansine demonstrated a tolerable safety profile at a dose of 80-170 mg/m2 in three different administration schedules in Japanese adults with metastatic solid tumors.