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

NCT04486378 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: BNT122-012020-000451-12U1111-1250-52942023-509516-28-00
• Study Type: interventional
• Target: 327
• Locations: 7 countries
• Sites: 90

Brief Summary

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.

Conditions

Colorectal Cancer Stage II; Colorectal Cancer Stage III

Keywords

Cancer; Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Relapse-free survival (RFS)

  Through study completion, up to 5 years

• Time to recurrence (TTR)

  Through study completion, up to 5 years

• Time to treatment failure (TTF)

  Through study completion, up to 5 years

• Overall survival (OS)

  Through study completion, up to 5 years

• Change of ctDNA status (approximately every 3 months)

  Through study completion, up to 5 years

Study Arms (5)

RO7198457

EXPERIMENTAL

Participants will receive a recommended dose of RO7198457.

Drug: RO7198457 intravenous (IV)

Observational Group

OTHER

Observational group will undergo watchful waiting, which is the standard of care in this setting.

Other: Observational group (no intervention)

Biomarker Cohort

EXPERIMENTAL

Drug: RO7198457 intravenous (IV)

Exploratory Cohort

EXPERIMENTAL

Drug: RO7198457 intravenous (IV)

Colorectal Liver Metastasis (CLM) Cohort

EXPERIMENTAL

Drug: RO7198457 intravenous (IV)

Interventions

RO7198457 intravenous (IV) DRUG

RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.

Biomarker Cohort; Colorectal Liver Metastasis (CLM) Cohort; Exploratory Cohort; RO7198457

Observational group (no intervention) OTHER

watchful waiting

Observational Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• BioNTech SE: lead
• Genentech, Inc.: collaborator

Study Sites (90)

John Muir Clinical Research Center

Concord, California, 94520, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Rocky Mountain Cancer Centers - Denver Midtwon

Denver, Colorado, 80218, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer

Indianapolis, Indiana, 46202, United States

Location

Allina Health

Minneapolis, Minnesota, 55407, United States

Location

Oncology Hematology Care Clinical Trials

Cincinnati, Ohio, 45245, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02906, United States

Location

Sarah Cannon (Tennessee Oncology - Nashville)

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A. - Austin

Austin, Texas, 78705, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology-San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Texas Oncology - Northeast Texas

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Northwest Cancer Specialists P.C.

Vancouver, Washington, 98684, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Imeldaziekenhuis General Hospital

Bonheiden, 2820, Belgium

Location

VZW Algemeen Ziekenhuis AZ Klina

Brasschaat, 2930, Belgium

Location

GHDC (Grand Hopital de Charleroi)

Charleroi, 6000, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

Centres Hospitaliers Jolimont

La Louvière, 7100, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, 3000, Belgium

Location

AZ Delta Roeselare

Roeselare, 8800, Belgium

Location

GasthuisZusters Antwerpen - Sint-Augustinus

Wilrijk, 2610, Belgium

Location

Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, 1200, Belgium

Location

The Ottawa Hospital Cancer Centre

Ottawa, K1H 8M2, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G 1X6, Canada

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitaetsklinikum St. Josef-Hospital Bochum

Bochum, 44791, Germany

Location

Universitätsklinikum Bonn, Med. Klinik u. Poliklinik I

Bonn, 53105, Germany

Location

Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)

Frankfurt am Main, 60488, Germany

Location

Studiengesellschaft BSF

Halle, 06108, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Hämatologisch-Onkologische Praxis Eppendorf

Hamburg, 20249, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

National Center for Tumor Diseases (NCT) Heidelberg

Heidelberg, 69120, Germany

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, 74078, Germany

Location

Universitaetsklinikum Leipzig AoeR

Leipzig, 04103, Germany

Location

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, 55131, Germany

Location

Klinikum der Philipps-Universität Marburg

Marburg, 35043, Germany

Location

LMU Klinikum (Campus Großhadern) Medizinische Klinik Universität München

München, 81377, Germany

Location

Städtisches Klinikum München GmbH, Klinikum Neuperlach

München, 81737, Germany

Location

OhO Ostholstein Onkologie

Oldenburg in Holstein, 23758, Germany

Location

Prosper Hospital

Recklinghausen, 45659, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, 15006, Spain

Location

Hospital Nuestra Senora de Sonsoles

Ávila, 05004, Spain

Location

Hospital Universitari Germans Trias - ICO Badalona

Badalona, 08916, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Clinic Hematolo/Oncologia- ICMHO, Hospital Clinic i Provincial de Barcelona

Barcelona, 8036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 8041, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HMN Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)

Madrid, 28050, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Regional Universitario Carlos Haya Malaga - Instituto de Investigacion Biomedica de Malaga

Málaga, 29011, Spain

Location

Complejo Hospitalario de Orense

Ourense, 32005, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Complejo Hospitalario de Navarra (CHN)

Pamplona, 31008, Spain

Location

Hospital Universitario Marques De Valdecilla

Santander, 39008, Spain

Location

Complejo Hospitalario Universitario De Santiago De Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen del Rocio - Hospital de la Mujer

Seville, 41013, Spain

Location

Consorcio Hospital General Valencia

Valencia, 46014, Spain

Location

Complexo Hospitalario Universitario de Vigo (CHUVI)

Vigo, 36312, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)

Lund, 221 00, Sweden

Location

Sodersjukhuset, Onkologiska Kliniken

Stockholm, 11883, Sweden

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, CH63 4JY, United Kingdom

Location

Queen Elizabeth Hospital Birmingham-University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2GW, United Kingdom

Location

Velindre NHS Trust, Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

Dorset County Hospital NHS Foundation Trust - Dorset County Hospital

Dorchester, DT1 2JY, United Kingdom

Location

Beatson West of Scotland Cancer Centre - Gartnavel Royal Hospital - NHS Greater Glasgow and Clyde

Glasgow, G12 0XH, United Kingdom

Location

St Bartholomew's Hospital-Barts Health NHS Trust

London, EC1A 7BE, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW2 1PG, United Kingdom

Location

Guy's and St Thomas' Hospital NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

The Royal Marsden NHS Foundation Trust- Chelsea

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Churchill Hospital - Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

Location

Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust

Preston, PR2 9HT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM25NG, United Kingdom

Location

Torbay Hospital - South Devon Healthcare Nhs Foundation Trust, Lowes Bridge

Torquay, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 24, 2020
• Study Start: March 8, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (20); US (17); ES (24); SE (2); GB (16); BE (9); CA (2)