PMID- 38410109
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240229
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 14
DP  - 2024
TI  - Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, 
      and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients 
      with colorectal cancer (CoRe_CC-3).
PG  - 1351901
LID - 10.3389/fonc.2024.1351901 [doi]
LID - 1351901
AB  - INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer worldwide 
      in men and women. In the metastasized stage, treatment options and prognosis are 
      limited. To address the high medical need of this patient population, we 
      generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC 
      cells and on tumor vessels, thereby allowing for a "dual" anticancer effect. 
      METHODS AND ANALYSIS: This first-in-human clinical study is planned as a 
      prospective multicenter trial, enrolling patients with metastatic CRC after three 
      lines of therapy. During the dose-escalation part, initially, an accelerated 
      titration design with single-patient cohorts is employed. Here, each patient will 
      receive a fixed dose level (starting with 50 microg for the first patient); however, 
      between patients, dose level may be increased by up to 100%, depending on the 
      decision of a safety review committee. Upon occurrence of any adverse events 
      (AEs) grade >/=2, dose-limiting toxicity (DLT), or reaching a dose level of >/=800 
      microg, the escalation will switch to a standard 3 + 3 dose design. After maximum 
      tolerated dose (MTD) has been determined, defined as no more than one of the six 
      patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD 
      level in the dose-expansion phase. Primary endpoints are incidence and severity 
      of AEs, as well as the best objective response to the treatment according to 
      response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints 
      include overall safety, efficacy, survival, quality of life, and pharmacokinetic 
      investigations. ETHICS AND DISSEMINATION: The CD276xCD3 study was approved by the 
      Ethics Committee of the Medical Faculty of the Heinrich Heine University 
      Dusseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be 
      published in peer-reviewed journals. Trial registration numbers: 
      ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU 
      trial number 2022-503084-15-00).
CI  - Copyright (c) 2024 Jung, Schlenk, Hackenbruch, Roldan Pinzon, Bitzer, Pflugler, 
      Walz, Jung, Heitmann and Salih.
FAU - Jung, Susanne
AU  - Jung S
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed 
      Tumor Therapies', University of Tubingen, Tubingen, Germany.
AD  - Department of Peptide-based Immunotherapy, Institute of Immunology, University of 
      Tubingen and University Hospital Tubingen, Tubingen, Germany.
FAU - Schlenk, Richard F
AU  - Schlenk RF
AD  - NCT Trial Center, National Center for Tumor Diseases (NCT), German Cancer 
      Research Center (DKFZ) and Heidelberg University Hospital, Heidelberg, Germany.
AD  - Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, 
      Germany.
FAU - Hackenbruch, Christopher
AU  - Hackenbruch C
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed 
      Tumor Therapies', University of Tubingen, Tubingen, Germany.
AD  - Department of Peptide-based Immunotherapy, Institute of Immunology, University of 
      Tubingen and University Hospital Tubingen, Tubingen, Germany.
FAU - Roldan Pinzon, Sandra S L
AU  - Roldan Pinzon SSL
AD  - NCT Trial Center, National Center for Tumor Diseases (NCT), German Cancer 
      Research Center (DKFZ) and Heidelberg University Hospital, Heidelberg, Germany.
FAU - Bitzer, Michael
AU  - Bitzer M
AD  - Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, 
      Infectiology and Geriatrics, University Hospital Tubingen, Tubingen, Germany.
FAU - Pflugler, Martin
AU  - Pflugler M
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
FAU - Walz, Juliane S
AU  - Walz JS
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed 
      Tumor Therapies', University of Tubingen, Tubingen, Germany.
AD  - Department of Peptide-based Immunotherapy, Institute of Immunology, University of 
      Tubingen and University Hospital Tubingen, Tubingen, Germany.
FAU - Jung, Gundram
AU  - Jung G
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
FAU - Heitmann, Jonas S
AU  - Heitmann JS
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed 
      Tumor Therapies', University of Tubingen, Tubingen, Germany.
AD  - Department of Peptide-based Immunotherapy, Institute of Immunology, University of 
      Tubingen and University Hospital Tubingen, Tubingen, Germany.
FAU - Salih, Helmut R
AU  - Salih HR
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed 
      Tumor Therapies', University of Tubingen, Tubingen, Germany.
LA  - eng
PT  - Journal Article
DEP - 20240212
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10896605
OTO - NOTNLM
OT  - CD276
OT  - bispecific antibody
OT  - clinical trial
OT  - colorectal cancer
OT  - immunotherapy
OT  - translational immunology
COIS- GJ, HS, and MP are listed as inventors on the patent application "Antibodies 
      targeting, and other modulators of, the CD276 antigen, and uses thereof," 
      EP3822288A1, applicant is German Cancer Research Center, Heidelberg, and Medical 
      Faculty University of Tubingen, Germany. The remaining authors declare that the 
      research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2024/02/27 06:44
MHDA- 2024/02/27 06:45
PMCR- 2024/01/01
CRDT- 2024/02/27 03:33
PHST- 2023/12/07 00:00 [received]
PHST- 2024/01/22 00:00 [accepted]
PHST- 2024/02/27 06:45 [medline]
PHST- 2024/02/27 06:44 [pubmed]
PHST- 2024/02/27 03:33 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2024.1351901 [doi]
PST - epublish
SO  - Front Oncol. 2024 Feb 12;14:1351901. doi: 10.3389/fonc.2024.1351901. eCollection 
      2024.