A Study to Evaluate the Adverse Events, and Efficacy of Intravenous (IV) of Telisotuzumab Adizutecan in Combination With IV Oxaliplatin, Fluorouracil, Folinic Acid/Leucovorin, Bevacizumab, Panitumumab in Adult Participants With Metastatic Colorectal Cancer

Official title

A Phase 2, Open-Label, Randomized, Master Protocol Study to Evaluate Safety and Efficacy of Multiple Treatment Combinations With Telisotuzumab Adizutecan in Subjects With Metastatic Colorectal Cancer

Overview

CRC is the third most common type of cancer diagnosed worldwide with developed countries at highest risk. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan is given in combination with oxaliplatin, fluorouracil (5FU), leucovorin (LV) (FOLFOX), and bevacizumab or panitumumab. Telisotuzumab adizutecan is an investigational drug being developed for the treatment of mCRC. Fluorouracil and leucovorin are drugs approved for the treatment of mCRC. This study will be divided into two stages, with the first stage treating participants with increasing doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU/LV and panitumumab until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into 3 groups called treatment arms where one group will receive one of two optimized doses of telisotuzumab adizutecan from the dose escalation phase with FOLFOX and bevacizumab or 5FU/LV and panitumumab, or a comparator of FOLFOX and bevacizumab or panitumumab. Approximately 390 adult participants with mCRC will be enrolled in the study in 100 sites worldwide. In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU/LV and panitumumab until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive 5FU/LV, but with one of two optimized doses of telisotuzumab adizutecan, or a comparator of FOLFOX and bevacizumab/pantitumumab. The study will run for a duration of approximately 6 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Interventions

• Drug Telisotuzumab Adizutecan
  Intravenous (IV) Infusion
• Drug Fluorouracil
  IV Infusion; IV Injection
• Drug Oxaliplatin
  IV Infusion
• Drug Leucovorin
  IV Infusion; IV Injection
• Drug Bevacizumab
  IV Infusion
• Drug Panitumumab
  IV Infusion

Primary outcome measures

• Objective Response (OR) as Assessed by the Investigator confirmed complete response (CR) or partial response (PR) as assessed by the investigator per response evaluation criteria in solid tumors (RECIST), version 1.1. [Time frame: Up to 24 Weeks]
• Number of Participants with Adverse Events (AE)s [Time frame: Up to Approximately 6 Years]

Secondary outcome measures (4)

• Progression-Free Survival (PFS) as Assessed by the Investigator [Time frame: Up to 22 Months]
• Duration of Response (DOR) as Assessed by the investigator [Time frame: Up to 14 Months]
• Overall Survival (OS) [Time frame: Up to Approximately 6 Years]
• Disease Control (DC) as Assessed by the Investigator [Time frame: Up to Approximately 6 Years]

Eligibility criteria

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Laboratory values meeting the criteria within the protocol.
• Has measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.

Exclusion criteria

• Prior systemic regimen containing c-Met targeting agent(s) (e.g., antibody, antibody drug conjugate, bispecific) and/or any topoisomerase inhibitor(s) (e.g., irinotecan).
• History of other malignancies within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death.

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 · 16 centers

• City of Hope National Medical Center /ID# 270255 — Duarte
• UCLA - Santa Monica /ID# 270621 — Santa Monica
• Yale New Haven Hospital /ID# 270565 — New Haven
• Northwest Georgia Oncology Centers /ID# 270245 — Marietta
• University of Chicago Medical Center /ID# 271688 — Chicago
• Hope And Healing Cancer Services /ID# 271562 — Hinsdale
• Dana-Farber Cancer Institute /ID# 270624 — Boston
• University Of Michigan /ID# 270790 — Ann Arbor
• … and 8 more centers

Brazil · 6 centers

• Hospital Sao Rafael /ID# 271681 — Salvador
• Oncosite - Centro de Pesquisa Clinica em Oncologia /ID# 270147 — Ijuí
• Hospital De Amor /ID# 271874 — Barretos
• Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 271651 — São José do Rio Preto
• Instituto D'Or de Pesquisa e Ensino - Regional Sao Paulo /ID# 270546 — São Paulo
• Nucleo De Pesquisa Clinica Da Rede Sao Camilo /ID# 272311 — São Paulo

Taiwan · 6 centers

• Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 269724 — Kaohsiung City
• Kaohsiung Chang Gung Memorial Hospital /ID# 269726 — Kaohsiung City
• National Cheng Kung University Hospital /ID# 270835 — Tainan
• National Taiwan University Hospital /ID# 269717 — Taipei
• Taipei Veterans General Hospital /ID# 269718 — Taipei
• Linkou Chang Gung Memorial Hospital /ID# 269725 — Taoyuan City

Australia · 5 centers

• Macquarie University /ID# 271514 — Sydney
• Mater Hospital Brisbane /ID# 270694 — South Brisbane
• The Queen Elizabeth Hospital /ID# 270693 — Woodville South
• Austin Health /ID# 270692 — Heidelberg
• One Clinical Research /ID# 270695 — Nedlands

Israel · 5 centers

• Rabin Medical Center. /ID# 268008 — Petah Tikva
• Tel Aviv Sourasky Medical Center /ID# 268010 — Tel Aviv
• Rambam Health Care Campus- Haifa /ID# 268006 — Haifa
• Shaare Zedek Medical Center /ID# 268009 — Jerusalem
• Hadassah Medical Center-Hebrew University /ID# 268007 — Jerusalem

Japan · 5 centers

• Aichi Cancer Center /ID# 270113 — Nagoya
• National Cancer Center Hospital East /ID# 270114 — Kashiwa-shi
• St Marianna University School Of Medicine /ID# 270111 — Kawasaki-shi
• Tohoku University Hospital /ID# 270966 — Sendai
• National Cancer Center Hospital /ID# 270112 — Chuo-Ku

Canada · 3 centers

• Arthur J.E Child Comprehensive Cancer Centre /ID# 269809 — Calgary
• London Health Sciences Centre - Victoria Hospital & Children's Hospital /ID# 270680 — London
• Princess Margaret Cancer Centre /ID# 268715 — Toronto

France · 3 centers

• Chu De Lille - Hopital Claude Huriez /ID# 270222 — Lille
• Centre Hospitalier Universitaire de Poitiers /ID# 270225 — Poitiers
• Hopital Europeen Georges Pompidou /ID# 270224 — Paris

Czechia · 2 centers

• Fakultni Thomayerova nemocnice /ID# 269632 — Prague
• Fakultni nemocnice Hradec Kralove - Sokolska /ID# 268773 — Hradec Králové

Greece · 2 centers

• St. Luke's Hospital /ID# 269963 — Panórama
• Theagenio Cancer Hospital /ID# 269640 — Thessaloniki

Puerto Rico · 2 centers

• Pan American Center for Oncology Trials - Rio Piedras /ID# 268809 — Rio Piedras
• Puerto Rico Medical Research Center /ID# 268825 — San Juan

Spain · 2 centers

• Hospital Universitario Marques de Valdecilla /ID# 269732 — Santander
• Hospital Universitario Vall de Hebron /ID# 270191 — Barcelona

Austria · 1 center

• Medizinische Universitaet Wien /ID# 268872 — Vienna

United Kingdom · 1 center

• The Royal Marsden - Sutton /ID# 271172 — Sutton

Identifiers

NCT: NCT06820463 · M24-533 · EU CT · 2024-512981-33-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗