A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients With ctDNA-positive, Resected Stage II (High Risk) and Stage III Colorectal Cancer

A Multi-site, Open-label, Phase II, Randomized, Controlled Trial to Compare the Efficacy of RO7198457 Versus Watchful Waiting in Resected, Stage II (High Risk) and Stage III Colorectal Cancer Patients Who Are ctDNA Positive Following Resection

This is a multi-site, open-label, Phase II, randomized, trial to compare the efficacy of RO7198457 versus watchful waiting in patients with circulating tumor DNA (ctDNA) positive, surgically resected Stage II/III rectal cancer, or Stage II (high risk)/Stage III colon cancer.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Stage II; Colorectal Cancer Stage III
• Intervention / Treatment: Drug: RO7198457 intravenous (i.v.); Other: Observational group (no intervention)

• Study Type: Interventional
• Enrollment (Estimated): 201
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Recruiting
    • Imeldaziekenhuis General Hospital
  • Brasschaat, Belgium, 2930
    • Recruiting
    • VZW Algemeen Ziekenhuis AZ Klina
  • Brussel, Belgium, 1070
    • Withdrawn
    • Institut Jules Bordet
  • Charleroi, Belgium, 6000
    • Recruiting
    • GHDC (Grand Hopital de Charleroi)
  • Kortrijk, Belgium, 8500
    • Recruiting
    • Az Groeninge
  • La Louviere, Belgium, 7100
    • Recruiting
    • Centres Hospitaliers Jolimont
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitaire Ziekenhuizen Leuven
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta Roeselare
  • Wilrijk, Belgium, 2610
    • Recruiting
    • GasthuisZusters Antwerpen - Sint-Augustinus
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Recruiting
    • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmedizin Berlin
  • Bochum, Germany, 44791
    • Recruiting
    • Universitaetsklinikum St. Josef-Hospital Bochum
  • Bonn, Germany, 53105
    • Recruiting
    • Universitätsklinikum Bonn, Med. Klinik u. Poliklinik I
  • Esslingen, Germany, 73730
    • Recruiting
    • Klinikum Esslingen GmbH
  • Frankfurt am Main, Germany, 60488
    • Recruiting
    • Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
  • Frankfurt am Main, Germany, 60590
    • Recruiting
    • Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
  • Halle, Germany, 06108
    • Recruiting
    • Studiengesellschaft BSF
  • Hamburg, Germany, 22763
    • Recruiting
    • Asklepios Klinik Altona
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitatsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 20249
    • Recruiting
    • Hämatologisch-Onkologische Praxis Eppendorf
  • Hannover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Recruiting
    • National Center for Tumor Diseases (NCT) Heidelberg
  • Heilbronn, Germany, 74078
    • Recruiting
    • SLK-Kliniken Heilbronn GmbH
  • Kiel, Germany, 24116
    • Recruiting
    • Staedtisches Krankenhaus Kiel gGmbH
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitaetsklinikum Leipzig AoeR
  • Mainz, Germany, 55131
    • Recruiting
    • Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
  • Marburg, Germany, 35043
    • Recruiting
    • Klinikum der Philipps-Universität Marburg
  • München, Germany, 81377
    • Recruiting
    • LMU Klinikum (Campus Großhadern) Medizinische Klinik Universität München
  • München, Germany, 81737
    • Recruiting
    • Städtisches Klinikum München GmbH, Klinikum Neuperlach
  • Oldenburg In Holstein, Germany, 23758
    • Recruiting
    • OhO Ostholstein Onkologie
  • Recklinghausen, Germany, 45659
    • Recruiting
    • Prosper Hospital
  • Stuttgart, Germany, 70376
    • Recruiting
    • Robert-Bosch-Krankenhaus - Centrum fuer Tumorerkrankungen
  • Ulm, Germany, 89081
    • Recruiting
    • Universitätsklinikum Ulm
  • Würzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg
• Spain
  • A Coruna, Spain, 15006
    • Recruiting
    • Complejo Hospitalario Universitario A Coruña
  • Avila, Spain, 05004
    • Recruiting
    • Hospital Nuestra Señora de Sonsoles
  • Badalona, Spain, 08916
    • Recruiting
    • Hospital Universitari Germans Trias - ICO Badalona
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8041
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 8036
    • Recruiting
    • Institut Clinic Hematolo/Oncologia- ICMHO, Hospital Clinic i Provincial de Barcelona
  • Cordoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28027
    • Recruiting
    • Clínica Universidad Navarra
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HMN Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Majadahonda, Spain, 28222
    • Recruiting
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • Málaga, Spain, 29011
    • Recruiting
    • Hospital Regional Universitario Carlos Haya Malaga - Instituto de Investigacion Biomedica de Malaga
  • Orense, Spain, 32005
    • Recruiting
    • Complejo Hospitalario de Orense
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universitaria de Navarra
  • Pamplona, Spain, 31008
    • Recruiting
    • Complejo Hospitalario de Navarra (CHN)
  • Santander, Spain, 39008
    • Recruiting
    • Hospital Universitario Marqués de Valdecilla
  • Santiago De Compostela, Spain, 15706
    • Recruiting
    • Complejo Hospitalario Universitario de Santiago de Compostela
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio - Hospital de la Mujer
  • Valencia, Spain, 46014
    • Recruiting
    • Consorcio Hospital General Valencia
  • Vigo, Spain, 36312
    • Recruiting
    • Complexo Hospitalario Universitario de Vigo (CHUVI)
  • Zaragoza, Spain, 50009
    • Recruiting
    • Hospital Universitario Miguel Servet
• Sweden
  • Lund, Sweden, 221 00
    • Recruiting
    • Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)
  • Stockholm, Sweden, 17176
    • Recruiting
    • Karolinska Universitetssjukhuset Solna
  • Stockholm, Sweden, 11883
    • Recruiting
    • Sodersjukhuset, Onkologiska Kliniken
• United Kingdom
  • Bebington, United Kingdom, CH63 4JY
    • Recruiting
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • Birmingham, United Kingdom, B15 2GW
    • Recruiting
    • Queen Elizabeth Hospital Birmingham-University Hospitals Birmingham NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 2TL
    • Recruiting
    • Velindre NHS Trust, Velindre Cancer Centre
  • Glasgow, United Kingdom, G12 0XH
    • Recruiting
    • Beatson West of Scotland Cancer Centre - Gartnavel Royal Hospital - NHS Greater Glasgow and Clyde
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's and St Thomas' Hospital NHS Foundation Trust
  • London, United Kingdom, NW2 1PG
    • Recruiting
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • The Royal Marsden NHS Foundation Trust- Chelsea
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St Bartholomew's Hospital-Barts Health NHS Trust
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital
  • Preston, United Kingdom, PR2 9HT
    • Recruiting
    • Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
  • Sutton, United Kingdom, SM25NG
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
  • Torquay, United Kingdom, TQ2 7AA
    • Recruiting
    • Torbay Hospital - South Devon Healthcare Nhs Foundation Trust, Lowes Bridge
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic - Scottsdale
  • California
    • Concord, California, United States, 94520
      • Recruiting
      • John Muir Clinical Research Center
    • Glendale, California, United States, 91204
      • Recruiting
      • The Oncology Institute of Hope and Innovation
    • Greenbrae, California, United States, 94904
      • Recruiting
      • Marin Cancer Care
    • Orange, California, United States, 92868
      • Recruiting
      • St Joseph Hospital of Orange
    • Santa Barbara, California, United States, 93105
      • Recruiting
      • Sansum Clinic
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Rocky Mountain Cancer Centers - Denver Midtwon
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Recruiting
      • Florida Cancer Specialist South
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
    • West Palm Beach, Florida, United States, 33401
      • Withdrawn
      • Florida Cancer Specialists
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Recruiting
      • Cancer Care Center of Decatur, Cancer Care Specialists of IL
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Comprehensive Cancer
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville - James Graham Brown Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Josephine Ford Cancer Center-Henry Ford Cancer Center
  • New York
    • Albany, New York, United States, 12206
      • Recruiting
      • New York Oncology Hematology, P.C.
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medical College
    • New York, New York, United States, 10032
      • Recruiting
      • New York - Presbyterian Hospital - Columbia University Medical center
    • Rochester, New York, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Recruiting
      • Oncology Hematology Care Clinical Trials
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Willamette Valley Cancer Institute and Research Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Recruiting
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Hollings Cancer Center Medical University Of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon (Tennessee Oncology - Nashville
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Oncology, P.A. - Austin
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78240
      • Recruiting
      • Texas Oncology-San Antonio Medical Center
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology - Northeast Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington
    • Seattle, Washington, United States, 98101
      • Recruiting
      • Benaroya Research Institute at Virginia Mason
    • Spokane, Washington, United States, 99218
      • Recruiting
      • MultiCare Institute for Research & Innovation
    • Vancouver, Washington, United States, 98684
      • Recruiting
      • Northwest Cancer Specialists P.C.
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital and Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be a man or woman of at least 18 years of age.

• Patients must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III colon cancer per AJCC 2017 that has been surgically totally resected (R0 confirmed by pathology report). Stage II (high risk) colon cancer is defined as Stage II disease with any of the following risk factors for recurrence:

  • T4
  • Grade ≥ 3.
  • Clinical presentation with bowel obstruction or perforation.
  • Histological signs of vascular, lymphatic or perineural invasion.
  • < 12 nodes examined.

• Patients must have detectable ctDNA prior to start of adjuvant chemotherapy (AdCTx) (except for the Biomarker Cohort).

  • ctDNA assay must be performed through this trial or study BNT000-001 ctDNA screening protocol.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Patients must have adequate hematologic and organ function.
• Adequate tumor material in formalin-fixed paraffin embedded (FFPE) blocks or as sectioned tissue (only upon approval by sponsor) must be available (as described in the laboratory manual).
• The patient has started a standard of care AdCTx within 8 weeks post-surgery and has completed at least 3 months of treatment of a 3 or a 6 month course of chemotherapy (including rest days).

Exclusion Criteria:

• Patients with uncontrolled intercurrent illness.
• Diagnosed microsatellite instability (MSI) high tumors.

• Prior therapy with any of the following:

  • Neo-adjuvant (radio)chemotherapy prior to surgery.
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of trial treatment or anticipation of need for systemic immunosuppressive medication during trial treatment, with the exception of low dose steroids defined as 10 mg oral prednisone (or equivalent).
  • Current or recent (within the 28 days prior to randomization) treatment with another investigational drug.
• Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
• Patients who developed metastatic disease during screening/receiving standard of care treatment (not applicable for Exploratory Cohort).

• Patients with known past or current malignancy other than inclusion diagnosis, except for:

  • Cervical carcinoma of Stage 1B or less.
  • Non-invasive basal cell or squamous cell skin carcinoma.
  • Non-invasive, superficial bladder cancer.
  • Prostate cancer with a current PSA level < 0.1 ng/mL.
  • Any curable cancer with a complete response (CR) of > 2 years duration.
• Patients with known allergies, hypersensitivity, or intolerance to RO7198457 or its excipients.
• Patients who had major surgery (e.g., surgery requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or have surgery planned during the time the patient are expected to participate in the trial.
• Patients with active hepatitis B or C.
• Patients who have a history of human immunodeficiency virus (HIV) antibody positivity, or tests positive for HIV at screening.
• Patients who have had prior splenectomy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7198457; Participants will receive a recommended dose of RO7198457.	Drug: RO7198457 intravenous (i.v.); RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.
Other: Observational Group; Observational group will undergo watchful waiting, which is the standard of care in this setting.	Other: Observational group (no intervention); watchful waiting
Experimental: Biomarker Cohort; 15 patients	Drug: RO7198457 intravenous (i.v.); RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.
Experimental: Exploratory Cohort; 20 patients	Drug: RO7198457 intravenous (i.v.); RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	DFS defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by an independent central radiology assessment.; Occurrence of second primary (same or other) cancer as determined by an independent central radiology assessment.; Death from any cause.; Loss to follow-up is censored.	Through study completion, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS)	RFS is defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by the investigator.; Death from any cause.; Occurrence of second primary (same or other) cancer as determined by the investigator is ignored.; Loss to follow-up is censored.	Through study completion, up to 5 years
Time to recurrence (TTR)	TTR is defined as the time from randomization to occurrence of any of the following events (i.e., events related to the same cancer), whichever occurs first: Locoregional recurrence or distant metastases as determined by the investigator.; Death from same cancer.; Occurrence of second primary (same or other) cancer as determined by the investigator is ignored.; Loss to follow-up and deaths from other cancer, non-cancer-related deaths, treatment-related deaths are censored.	Through study completion, up to 5 years
Time to treatment failure (TTF)	TTF is defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by the investigator.; Occurrence of second primary (same or other) cancer as determined by the investigator.; Death from any cause except non-cancer related death.; Loss to follow-up and non-cancer-related deaths are censored.	Through study completion, up to 5 years
Overall survival (OS)	OS defined as the time from randomization to death from any cause.	Through study completion, up to 5 years
Change of Circulating tumor DNA (ctDNA) status (every 3 months)		Through study completion, up to 5 years
Occurrence of treatment emergent adverse event (TEAE)	TEAE, including Grade 3+, serious, fatal TEAE by relationship (AEs graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events, version 5.0 [CTCAE v5.0])	15 months
Occurrence of dose reduction and discontinuation of IMP due to a TEAE.		15 months

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: BNT122-01; 2020-000451-12 (EudraCT Number); U1111-1250-5294 (Other Identifier: WHO Universal Trial Number (UTN))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No