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: Active, not recruiting
• Conditions: Colorectal Cancer Stage II; Colorectal Cancer Stage III
• Intervention / Treatment: Other: Observational group (no intervention); Drug: RO7198457 intravenous (IV)

Detailed Description

Patients will receive up to 15 doses of RO7198457 over the course of trial treatment.

• Study Type: Interventional
• Enrollment (Estimated): 327
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis General Hospital
  • Brasschaat, Belgium, 2930
    • VZW Algemeen Ziekenhuis AZ Klina
  • Charleroi, Belgium, 6000
    • GHDC (Grand Hopital de Charleroi)
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
  • La Louvière, Belgium, 7100
    • Centres Hospitaliers Jolimont
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven
  • Roeselare, Belgium, 8800
    • AZ Delta Roeselare
  • Wilrijk, Belgium, 2610
    • GasthuisZusters Antwerpen - Sint-Augustinus
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
• Canada
  • Ottawa, Canada, K1H 8M2
    • The Ottawa Hospital Cancer Centre
  • Toronto, Canada, M5G 1X6
    • Princess Margaret Cancer Centre
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Bochum, Germany, 44791
    • Universitaetsklinikum St. Josef-Hospital Bochum
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn, Med. Klinik u. Poliklinik I
  • Frankfurt am Main, Germany, 60488
    • Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
  • Halle, Germany, 06108
    • Studiengesellschaft BSF
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Hamburg, Germany, 20249
    • Hämatologisch-Onkologische Praxis Eppendorf
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • National Center For Tumor Diseases (NCT) Heidelberg
  • Heilbronn, Germany, 74078
    • SLK-Kliniken Heilbronn GmbH
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig AoeR
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
  • Marburg, Germany, 35043
    • Klinikum der Philipps-Universität Marburg
  • München, Germany, 81377
    • LMU Klinikum (Campus Großhadern) Medizinische Klinik Universität München
  • München, Germany, 81737
    • Städtisches Klinikum München GmbH, Klinikum Neuperlach
  • Oldenburg in Holstein, Germany, 23758
    • OhO Ostholstein Onkologie
  • Recklinghausen, Germany, 45659
    • Prosper Hospital
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias - ICO Badalona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8041
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 8036
    • Institut Clinic Hematolo/Oncologia- ICMHO, Hospital Clinic i Provincial de Barcelona
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28050
    • Hospital Universitario HMN Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • Málaga, Spain, 29011
    • Hospital Regional Universitario Carlos Haya Malaga - Instituto de Investigacion Biomedica de Malaga
  • Ourense, Spain, 32005
    • Complejo Hospitalario de Orense
  • Pamplona, Spain, 31008
    • Clinica Universitaria de Navarra
  • Pamplona, Spain, 31008
    • Complejo Hospitalario de Navarra (CHN)
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago de Compostela
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio - Hospital de la Mujer
  • Valencia, Spain, 46014
    • Consorcio Hospital General Valencia
  • Vigo, Spain, 36312
    • Complexo Hospitalario Universitario de Vigo (CHUVI)
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Ávila, Spain, 05004
    • Hospital Nuestra Señora de Sonsoles
• Sweden
  • Lund, Sweden, 221 00
    • Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)
  • Stockholm, Sweden, 11883
    • Sodersjukhuset, Onkologiska Kliniken
• United Kingdom
  • Bebington, United Kingdom, CH63 4JY
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth Hospital Birmingham-University Hospitals Birmingham NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre NHS Trust, Velindre Cancer Centre
  • Cottingham, United Kingdom, HU16 5JQ
    • Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
  • Dorchester, United Kingdom, DT1 2JY
    • Dorset County Hospital NHS Foundation Trust - Dorset County Hospital
  • Glasgow, United Kingdom, G12 0XH
    • Beatson West of Scotland Cancer Centre - Gartnavel Royal Hospital - NHS Greater Glasgow and Clyde
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' Hospital NHS Foundation Trust
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital-Barts Health NHS Trust
  • London, United Kingdom, NW2 1PG
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust- Chelsea
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital - Oxford University Hospitals NHS Foundation Trust
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
  • Sutton, United Kingdom, SM25NG
    • The Royal Marsden NHS Foundation Trust
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital - South Devon Healthcare Nhs Foundation Trust, Lowes Bridge
• United States
  • California
    • Concord, California, United States, 94520
      • John Muir Clinical Research Center
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers - Denver Midtwon
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Comprehensive Cancer
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Oncology Hematology Care Clinical Trials
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon (Tennessee Oncology - Nashville)
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology, P.A. - Austin
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78240
      • Texas Oncology-San Antonio Medical Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Northeast Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists P.C.
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

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 American Joint Committee on Cancer (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 evaluated after surgery.

    • For the CLM Cohort: patients must have metastatic colorectal cancer (mCRC) (Stage IV) with resected CLM (synchronous and metachronous CLM within 6 months of initial diagnosis) per AJCC 2017, after standard of care (SoC) primary resection and curative-intent hepatectomy (R0 confirmed by pathology report) with or without (neo-)adjuvant chemotherapy (prior to hepatectomy), and planned adjuvant chemotherapy.
    • For the Biomarker Cohort: patients with tumors of the colon, including but not limited to, colon adenocarcinoma, carcinoid tumors (including goblet cell carcinoid/adenocarcinoma), and tumors of the appendix, whose tumors were surgically resected and are planned for adjuvant chemotherapy (per institutional standards), can be included.

• 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 Performance Status of 0-1.
• Patients must have adequate hematologic, bone marrow and organ function as defined by the protocol.
• Adequate tumor material in formalin-fixed paraffin embedded blocks or as sectioned tissue (only upon approval by sponsor) must be available (as described in the laboratory manual). For the CLM Cohort: tumor material must come from primary resection for patients who undergo staged approach, or from available archival material from the previously untreated tumor biopsy from the primary.
• At least 5 tumor neoantigens identified in the provided tumor sample.
• The patient has started a standard of care AdCTx preferably within 8 weeks but no later than 10 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). For the CLM Cohort: patient must have completed AdCTx with or without (neo-)adjuvant chemotherapy for up to 6 months in total or total intended amount determined by care providers per SoC. AdCTx must have started preferably within 8 weeks, but no later than 10 weeks, after hepatectomy. For the Biomarker Cohort: patient must have received at least one cycle of adjuvant chemotherapy per institutional standards.

Exclusion Criteria:

• Patients with uncontrolled intercurrent illness as defined by the protocol.
• Diagnosed microsatellite instability 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.

    • Exception for the CLM Cohort: primary tumor must be resected and (neo-)adjuvant chemotherapy prior to curative-intent hepatectomy is accepted.
• 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 the Exploratory Cohort or the Biomarker 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 prostate-specific antigen level < 0.1 ng/mL.
  • Any curable cancer with a complete response 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 positive serology for hepatitis B indicative of active hepatitis B infection:

  • Positive test for hepatitis B surface antigen (HBsAg) OR

  • Negative test for HBsAg AND positive test for antibodies to hepatitis B core antigens (anti-HBc) AND positive test for hepatitis B virus (HBV) DNA.

    • Serological markers indicative of vaccination (isolated antibodies to hepatitis B surface antigens [anti-HBs]) or resolved natural infection without viral load (anti-HBc with negative HBsAg and negative HBV DNA) are not exclusionary.
• Active Hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
• 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.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7198457; Participants will receive a recommended dose of RO7198457.	Drug: RO7198457 intravenous (IV); 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: Exploratory Cohort	Drug: RO7198457 intravenous (IV); RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.
Experimental: Biomarker Cohort	Drug: RO7198457 intravenous (IV); RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.
Experimental: Colorectal Liver Metastasis (CLM) Cohort	Drug: RO7198457 intravenous (IV); 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
Overall survival (OS)	OS defined as the time from randomization to death from any cause.	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.; Start of new cancer therapy.; Loss to follow-up and non-cancer-related deaths are censored.	Through study completion, up to 5 years
Change of ctDNA status (approximately 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 (adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0).	15 months
Occurrence of dose reduction and discontinuation of RO7198457 due to a TEAE.		15 months

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: Genentech, Inc.
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): August 1, 2030

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 (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Colorectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplasms; Colorectal Neoplasms
• Other Study ID Numbers: BNT122-01; 2020-000451-12 (EudraCT Number); U1111-1250-5294 (Other Identifier: WHO Universal Trial Number (UTN)); 2023-509516-28-00 (Ctis)

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