Title
A randomized, open label, 3-arm Phase 3 study of precemtabart tocentecan with or without bevacizumab compared to trifluridine/tipiracil plus bevacizumab in participants with previously treated metastatic colorectal cancer (PROCEADE-CRC-03)

Description
A Randomized, Open Label, 3-arm Phase 3 Study of Precemtabart Tocentecan With or Without Bevacizumab Compared to Trifluridine/Tipiracil Plus Bevacizumab in Participants With Previously Treated Metastatic Colorectal Cancer (PROCEADE-CRC-03)

Objective
To demonstrate improvement in OS with Precem-TcT as single agent compared to FTD-TPI plus bevacizumab.
To demonstrate improvement in OS with Precem-TcT in combination with bevacizumab compared to FTD-TPI plus bevacizumab.
Secondary:
To evaluate OS of Precem-TcT as single agent and of Precem-TcT in combination with bevacizumab.
To demonstrate improvement in PFS with Precem-TcT as single agent compared to FTD-TPI plus bevacizumab.
To demonstrate improvement in PFS with Precem-TcT in combination with bevacizumab compared to FTD-TPI plus bevacizumab.
To evaluate PFS of Precem-TcT as single agent and of Precem-TcT in combination with bevacizumab.
To assess improvement in OR with Precem-TcT as single agent compared to FTD-TPI plus bevacizumab.
To assess improvement in OR with Precem-TcT in combination with bevacizumab compared to FTD-TPI plus bevacizumab.
To evaluate OR of Precem-TcT as single agent and of Precem-TcT in combination with bevacizumab.
To evaluate DoR of Precem-TcT as single agent and of FTD-TPI plus bevacizumab.
To evaluate DoR of Precem-TcT in combination with bevacizumab and of FTD-TPI plus bevacizumab.
To evaluate DoR of Precem-TcT as single agent and of Precem-TcT in combination with bevacizumab.
To evaluate the safety and tolerability with Precem-TcT as single agent compared to FTD-TPI plus bevacizumab.
To evaluate the safety and tolerability with Precem-TcT in combination with bevacizumab compared to FTD-TPI plus bevacizumab.
To evaluate the safety and tolerability with Precem-TcT as single agent compared to Precem-TcT in combination with bevacizumab.
To characterize the PK profile of Precem-TcT (conjugated antibody and unconjugated payload) as single agent or in combination with bevacizumab.
To characterize the immunogenicity of Precem-TcT.
To evaluate quality of life with Precem-TcT as single agent or Precem-TcT in combination with bevacizumab compared to FTD-TPI plus bevacizumab using EORTC QLQ-C30 during the investigational treatment phase.

Treatment This study aims to address the unmet medical need of participants with metastatic colorectal cancer (mCRC) who have previously been treated with irinotecan, oxaliplatin, a fluoropyrimidine, and bevacizumab, by demonstrating an overall survival prolongation with precemtabart tocentecan (Precem-TcT) as single agent or Precem-TcT in combination with bevacizumab compared to trifluridine/tipiracil (FTD-TPI) plus bevacizumab.

Key Eligibility Inclusion Criteria:
- Participants with documented histopathological diagnosis of metastatic colorectal cancer, who were intolerant to, or whose disease was refractory to, or progressed after standard systemic therapies and no more than 2 previous systemic treatment regimens in the metastatic setting.
- Participants must have received and progressed on no more than 2 previous systemic treatment regimens in the metastatic setting
- Eastern Cooperative Oncology Group (ECOG) performance status less than equal to 1
- Participants must be able to swallow oral tablets, and to comply with the study requirements for all scheduled evaluations
- Other protocol defined inclusion criteria may apply

Exclusion Criteria:
- If Adverse Events related to previous therapies have not recovered to less than Grade 1 by National Cancer Institute - Common Terminology Criteria for Adverse Events version 6.0
- Participant has a history of additional malignancy within 3 years before randomization
- Participants with known brain metastases
- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months prior to randomization
- Participants with ileus of more than Grade 1, or chronic inflammatory bowel disease (example ulcerative colitis, Crohn's disease) and/or bowel obstruction, or participants with chronic gastrointestinal disorders that, in the Investigator's opinion, might significantly interfere with proper absorption of the study treatments
- Other protocol defined exclusion criteria may apply

Applicable Disease Sites
Colon and Rectum

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital