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
- Conditions
- Colorectal Cancer Stage IIIColorectal Cancer Stage II
- Interventions
- Drug: RO7198457 intravenous (IV)Other: Observational group (no intervention)
- Registration Number
- NCT04486378
- Lead Sponsor
- BioNTech SE
- 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.
- Detailed Description
Patients will receive up to 15 doses of RO7198457 over the course of trial treatment.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 327
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Patients must be a man or woman of at least 18 years of age.
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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:
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T4
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Grade ≥ 3.
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Clinical presentation with bowel obstruction or perforation.
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Histological signs of vascular, lymphatic or perineural invasion.
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< 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.
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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.
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Patients must have an Eastern Cooperative Oncology Group Performance Status of 0-1.
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Patients must have adequate hematologic, bone marrow and organ function as defined by the protocol.
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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.
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At least 5 tumor neoantigens identified in the provided tumor sample.
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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.
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Patients with uncontrolled intercurrent illness as defined by the protocol.
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Diagnosed microsatellite instability high tumors.
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Prior therapy with any of the following:
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Neo-adjuvant (radio)chemotherapy prior to surgery.
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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).
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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.
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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.
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Patients who developed metastatic disease during screening/receiving standard of care treatment (not applicable for the Exploratory Cohort or the Biomarker Cohort).
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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.
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Patients with known allergies, hypersensitivity, or intolerance to RO7198457 or its excipients.
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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.
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Patients with positive serology for hepatitis B indicative of active hepatitis B infection:
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Positive test for hepatitis B surface antigen (HBsAg) OR
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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.
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Active Hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
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Patients who have a history of human immunodeficiency virus (HIV) antibody positivity, or tests positive for HIV at screening.
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Patients who have had prior splenectomy.
NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RO7198457 RO7198457 intravenous (IV) Participants will receive a recommended dose of RO7198457. Observational Group Observational group (no intervention) Observational group will undergo watchful waiting, which is the standard of care in this setting. Biomarker Cohort RO7198457 intravenous (IV) - Exploratory Cohort RO7198457 intravenous (IV) - Colorectal Liver Metastasis (CLM) Cohort RO7198457 intravenous (IV) -
- Primary Outcome Measures
Name Time Method Disease-free survival (DFS) Through study completion, up to 5 years 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.
- Secondary Outcome Measures
Name Time Method Change of ctDNA status (approximately every 3 months) Through study completion, up to 5 years Relapse-free survival (RFS) Through study completion, up to 5 years 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.Time to recurrence (TTR) Through study completion, up to 5 years 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.Time to treatment failure (TTF) Through study completion, up to 5 years 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.Overall survival (OS) Through study completion, up to 5 years OS defined as the time from randomization to death from any cause.
Occurrence of treatment emergent adverse event (TEAE) 15 months 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).
Occurrence of dose reduction and discontinuation of RO7198457 due to a TEAE. 15 months
Trial Locations
- Locations (118)
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)
🇸🇪Lund, Sweden
Sodersjukhuset, Onkologiska Kliniken
🇸🇪Stockholm, Sweden
Karolinska Universitetssjukhuset Solna
🇸🇪Stockholm, Sweden
Prosper Hospital
🇩🇪Recklinghausen, Germany
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Spain
Klinikum der Philipps-Universität Marburg
🇩🇪Marburg, Germany
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
National Center for Tumor Diseases (NCT) Heidelberg
🇩🇪Heidelberg, Germany
Mayo Clinic - Scottsdale
🇺🇸Scottsdale, Arizona, United States
John Muir Clinical Research Center
🇺🇸Concord, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Glendale, California, United States
Marin Cancer Care
🇺🇸Greenbrae, California, United States
St Joseph Hospital of Orange
🇺🇸Orange, California, United States
Sansum Clinic
🇺🇸Santa Barbara, California, United States
Rocky Mountain Cancer Centers - Denver Midtwon
🇺🇸Denver, Colorado, United States
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
Florida Cancer Specialist South
🇺🇸Fort Myers, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Florida Cancer Specialists
🇺🇸West Palm Beach, Florida, United States
SLK-Kliniken Heilbronn GmbH
🇩🇪Heilbronn, Germany
Cancer Care Center of Decatur, Cancer Care Specialists of IL
🇺🇸Decatur, Illinois, United States
Indiana University Melvin and Bren Simon Comprehensive Cancer
🇺🇸Indianapolis, Indiana, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
University of Louisville - James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Josephine Ford Cancer Center-Henry Ford Cancer Center
🇺🇸Detroit, Michigan, United States
Allina Health
🇺🇸Minneapolis, Minnesota, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
New York - Presbyterian Hospital - Columbia University Medical center
🇺🇸New York, New York, United States
Mayo Clinic Rochester
🇺🇸Rochester, New York, United States
Oncology Hematology Care Clinical Trials
🇺🇸Cincinnati, Ohio, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Hollings Cancer Center Medical University Of South Carolina
🇺🇸Charleston, South Carolina, United States
Sarah Cannon (Tennessee Oncology - Nashville
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute (SCRI) Oncology Partners
🇺🇸Nashville, Tennessee, United States
Texas Oncology, P.A. - Austin
🇺🇸Austin, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Oncology-San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Texas Oncology - Northeast Texas
🇺🇸Tyler, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Benaroya Research Institute at Virginia Mason
🇺🇸Seattle, Washington, United States
Staedtisches Krankenhaus Kiel gGmbH
🇩🇪Kiel, Germany
University of Washington
🇺🇸Seattle, Washington, United States
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
🇩🇪Mainz, Germany
MultiCare Institute for Research & Innovation
🇺🇸Spokane, Washington, United States
Northwest Cancer Specialists P.C.
🇺🇸Vancouver, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Froedtert Hospital and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
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, Belgium
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
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
Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
🇩🇪Frankfurt am Main, Germany
Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
🇩🇪Frankfurt am Main, Germany
Studiengesellschaft BSF
🇩🇪Halle, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Hämatologisch-Onkologische Praxis Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Leipzig AoeR
🇩🇪Leipzig, 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
Robert-Bosch-Krankenhaus - Centrum fuer Tumorerkrankungen
🇩🇪Stuttgart, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
Complejo Hospitalario Universitario A Coruna
🇪🇸A Coruna, Spain
Hospital Nuestra Senora de Sonsoles
🇪🇸Avila, Spain
Hospital Universitari Germans Trias - ICO Badalona
🇪🇸Badalona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Clinic Hematolo/Oncologia- ICMHO, Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Clinica Universidad Navarra
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario HMN Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)
🇪🇸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
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
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
St Bartholomew's Hospital-Barts Health NHS Trust
🇬🇧London, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Guy's and St Thomas' Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
The Royal Marsden NHS Foundation Trust- Chelsea
🇬🇧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
University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
🇬🇧Southampton, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
Torbay Hospital - South Devon Healthcare Nhs Foundation Trust, Lowes Bridge
🇬🇧Torquay, United Kingdom