A 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)

Official 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)

Overview

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 trifluoride/tipiracil (FTD-TPI) plus bevacizumab.

Interventions

• Drug Precemtabart tocentecan
  Precem-TcT, administered, once every 3 weeks intravenously, on Day 1 of each 21-day cycle.
• Drug Bevacizumab
  Bevacizumab, administered intravenously every 3 weeks on Day 1 of each 21-day cycle or every 2 weeks on Day 1 and Day 15 of each 28-day cycle.
• Drug Trifluridine/Tipiracil (FTD-TPI)
  FTD-TPI, tablet, administered orally twice daily, on Days 1 to 5 and Days 8 to 12 of each 28-day cycle.

Primary outcome measures

• Arm 1, 2 and 3: Overall Survival [Time frame: Time from date of randomization to death, assessed approximately up to average of 19 months]

Secondary outcome measures (9)

• Arm 1 and Arm 2: Overall Survival [Time frame: Time from date of randomization to death, assessed approximately up to average of 19 months]
• Progression Free Survival (PFS) [Time frame: Time from randomization to the first occurrence of disease progression or death, whichever occurs first (assessed up to average of 19 months)]
• Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator [Time frame: Up to average of 19 months]
• Duration of Response as Assessed by Investigator [Time frame: Time from first documentation of objective response to PD or death (assessed up to average of 19 months)]
• Number of Participants with Adverse Events (AEs) and Treatment Related Adverse Events [Time frame: Up to average of 19 months]
• Observed Concentration at End of Infusion (CEOI) Period [Time frame: At end of infusion on Cycle 1 Day 1 and Cycle 3 Day 1 (Arm 1 and Arm 2 only; each cycle is for 21 days)]
• Concentration Observed at the end of a Dosing Interval Immediately Before next Dosing (Ctrough) [Time frame: At end of dosing interval on Cycle1Day1,Cycle2Day1,Cycle3Day1,Cycle4Day1, Cycle5Day1,Cycle6Day1,Cycle7Day1 until treatment discontinuation(assessed up to average of 19months (Arm 1 and Arm 2 only; each cycle is for 21 days)]
• Number of Participants with Anti-Drug Antibody as measured by ADA assay [Time frame: Predose(-4to0 hours)on Cycle1Day1,Cycle2 Day1,Cycle 3Day1,Cycle4Day1, Cycle8Day1;thereafter every 4cycles until treatment discontinuation(assessed up to average of 19 months) (Arm 1 and Arm 2 only; each cycle is for 21 days)]
• Change from Baseline in Global Health Status, Physical, and Role Functioning Subscale Scores of European Organization for research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) [Time frame: Baseline, Cycle 1 Day 1 and Day 1 of every new cycle until treatment discontinuation (assessed up to average of 19 months).]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• Rocky Mountain Cancer Centers, LLP- Aurora — Lone Tree
• Illinois Cancer Specialists — Arlington Heights
• Illinois CancerCare PC — Peoria
• Springfield Clinic — Springfield
• Profound Research LLC at Cancer and Leukemia Center — Sterling Heights
• Minnesota Oncology Hematology, P.A. — Saint Louis Park
• Missouri Cancer Associates - 150518964 — Columbia
• SCRI Oncology Partners — Nashville
• … and 7 more centers

Australia · 2 centers

• GenesisCare North Shore (Oncology) — St Leonards
• Icon Cancer Centre Chermside — Chermside

Canada · 1 center

• University Health Network - Princess Margaret Cancer Centre — Toronto

Japan · 1 center

• National Cancer Center Hospital — Chūōku

South Korea · 1 center

• Samsung Medical Center — Seoul

Taiwan · 1 center

• China Medical University Hospital — Taichung

Identifiers

NCT: NCT07549412 · MS914001_0002 · 2025-524648-37-00 · CTR20262356 · jRCT2031260267

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20262356 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗