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

Colorectal Cancer Stage III Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04486378
• Other study ID #: BNT122-01
• Secondary ID: 2020-000451-12U1
• Status: Recruiting
• Phase: Phase 2
• Start date: March 8, 2021
• Est. completion date: July 2027

Study information

• Verified date: June 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 229
• Est. completion date: July 2027
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

• 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).

• 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).

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.

• 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 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 (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy):

• Based on a test for antibodies to hepatitis B core antigens (anti-HBc) and

• Negative test for antibodies to hepatitis B surface antigens (anti-HBs).

• 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.

Related Conditions & MeSH terms

• Colorectal Cancer Stage II
• Colorectal Cancer Stage III
• Colorectal Neoplasms

Intervention

Drug:
• RO7198457 intravenous (IV)
RO7198457 administered as an IV injection at protocol-specified intervals over 12 months.

Other:
• Observational group (no intervention)
watchful waiting

Locations

Country	Name	City	State
Belgium	Imeldaziekenhuis General Hospital	Bonheiden
Belgium	VZW Algemeen Ziekenhuis AZ Klina	Brasschaat
Belgium	Institut Jules Bordet	Brussel
Belgium	GHDC (Grand Hopital de Charleroi)	Charleroi
Belgium	AZ Groeninge	Kortrijk
Belgium	Centres Hospitaliers Jolimont	La Louviere
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Belgium	AZ Delta Roeselare	Roeselare
Belgium	GasthuisZusters Antwerpen - Sint-Augustinus	Wilrijk
Belgium	Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc	Woluwe-Saint-Lambert
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitaetsklinikum St. Josef-Hospital Bochum	Bochum
Germany	Universitätsklinikum Bonn, Med. Klinik u. Poliklinik I	Bonn
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt	Frankfurt am Main
Germany	Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)	Frankfurt am Main
Germany	Studiengesellschaft BSF	Halle
Germany	Asklepios Klinik Altona	Hamburg
Germany	Hämatologisch-Onkologische Praxis Eppendorf	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	National Center for Tumor Diseases (NCT) Heidelberg	Heidelberg
Germany	SLK-Kliniken Heilbronn GmbH	Heilbronn
Germany	Staedtisches Krankenhaus Kiel gGmbH	Kiel
Germany	Universitaetsklinikum Leipzig AoeR	Leipzig
Germany	Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR	Mainz
Germany	Klinikum der Philipps-Universität Marburg	Marburg
Germany	LMU Klinikum (Campus Großhadern) Medizinische Klinik Universität München	München
Germany	Städtisches Klinikum München GmbH, Klinikum Neuperlach	München
Germany	OhO Ostholstein Onkologie	Oldenburg In Holstein
Germany	Prosper Hospital	Recklinghausen
Germany	Robert-Bosch-Krankenhaus - Centrum fuer Tumorerkrankungen	Stuttgart
Germany	Universitätsklinikum Ulm	Ulm
Germany	Universitätsklinikum Würzburg	Würzburg
Spain	Complejo Hospitalario Universitario A Coruna	A Coruna
Spain	Hospital Nuestra Senora de Sonsoles	Avila
Spain	Hospital Universitari Germans Trias - ICO Badalona	Badalona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Clinic Hematolo/Oncologia- ICMHO, Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Clinica Universidad Navarra	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario HMN Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Majadahonda
Spain	Hospital Regional Universitario Carlos Haya Malaga - Instituto de Investigacion Biomedica de Malaga	Málaga
Spain	Complejo Hospitalario de Orense	Orense
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Complejo Hospitalario de Navarra (CHN)	Pamplona
Spain	Hospital Universitario Marques De Valdecilla	Santander
Spain	Complejo Hospitalario Universitario De Santiago De Compostela	Santiago De Compostela
Spain	Hospital Universitario Virgen del Rocio - Hospital de la Mujer	Sevilla
Spain	Consorcio Hospital General Valencia	Valencia
Spain	Complexo Hospitalario Universitario de Vigo (CHUVI)	Vigo
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)	Lund
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Sweden	Sodersjukhuset, Onkologiska Kliniken	Stockholm
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington
United Kingdom	Queen Elizabeth Hospital Birmingham-University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Velindre NHS Trust, Velindre Cancer Centre	Cardiff
United Kingdom	Beatson West of Scotland Cancer Centre - Gartnavel Royal Hospital - NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	Guy's and St Thomas' Hospital NHS Foundation Trust	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	St Bartholomew's Hospital-Barts Health NHS Trust	London
United Kingdom	The Royal Marsden NHS Foundation Trust- Chelsea	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust	Preston
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United Kingdom	Torbay Hospital - South Devon Healthcare Nhs Foundation Trust, Lowes Bridge	Torquay
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology, P.A. - Austin	Austin	Texas
United States	Hollings Cancer Center Medical University Of South Carolina	Charleston	South Carolina
United States	Oncology Hematology Care Clinical Trials	Cincinnati	Ohio
United States	John Muir Clinical Research Center	Concord	California
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Cancer Care Center of Decatur, Cancer Care Specialists of IL	Decatur	Illinois
United States	Rocky Mountain Cancer Centers - Denver Midtwon	Denver	Colorado
United States	Josephine Ford Cancer Center-Henry Ford Cancer Center	Detroit	Michigan
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Florida Cancer Specialist South	Fort Myers	Florida
United States	The Oncology Institute of Hope and Innovation	Glendale	California
United States	Marin Cancer Care	Greenbrae	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Melvin and Bren Simon Comprehensive Cancer	Indianapolis	Indiana
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon (Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Sarah Cannon Research Institute (SCRI) Oncology Partners	Nashville	Tennessee
United States	New York - Presbyterian Hospital - Columbia University Medical center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	St Joseph Hospital of Orange	Orange	California
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic Rochester	Rochester	New York
United States	Texas Oncology-San Antonio Medical Center	San Antonio	Texas
United States	Sansum Clinic	Santa Barbara	California
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	MultiCare Institute for Research & Innovation	Spokane	Washington
United States	Texas Oncology - Northeast Texas	Tyler	Texas
United States	Northwest Cancer Specialists P.C.	Vancouver	Washington
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
BioNTech SE	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	OS defined as the time from randomization to death from any cause.	Through study completion, up to 5 years
Secondary	Change of ctDNA status (approximately every 3 months)		Through study completion, up to 5 years
Secondary	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
Secondary	Occurrence of dose reduction and discontinuation of RO7198457 due to a TEAE.		15 months