Clinical trial NCT04486378: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Stage II
Colorectal Cancer Stage III
Keywords: Cancer
Colorectal Cancer
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2020-07-24
Enrollment: 327
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: Through study completion, up to 5 years
Secondary outcomes:
measure: Relapse-free survival (RFS)
timeFrame: Through study completion, up to 5 years
measure: Time to recurrence (TTR)
timeFrame: Through study completion, up to 5 years
measure: Time to treatment failure (TTF)
timeFrame: Through study completion, up to 5 years
measure: Overall survival (OS)
timeFrame: Through study completion, up to 5 years
measure: Change of ctDNA status (approximately every 3 months)
timeFrame: Through study completion, up to 5 years
measure: Occurrence of treatment emergent adverse event (TEAE)
timeFrame: 15 months
measure: Occurrence of dose reduction and discontinuation of RO7198457 due to a TEAE.
timeFrame: 15 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Concord
country: United States
facility: John Muir Clinical Research Center
state: California
city: Glendale
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Care
state: California
city: Orange
country: United States
facility: St Joseph Hospital of Orange
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Midtwon
state: Colorado
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialist South
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Decatur
country: United States
facility: Cancer Care Center of Decatur, Cancer Care Specialists of IL
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville - James Graham Brown Cancer Center
state: Kentucky
city: Detroit
country: United States
facility: Josephine Ford Cancer Center-Henry Ford Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health
state: Minnesota
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: New York - Presbyterian Hospital - Columbia University Medical center
state: New York
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Hollings Cancer Center Medical University Of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon (Tennessee Oncology - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI) Oncology Partners
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology, P.A. - Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Medical Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists P.C.
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital and Medical College of Wisconsin
state: Wisconsin
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis General Hospital
city: Brasschaat
country: Belgium
facility: VZW Algemeen Ziekenhuis AZ Klina
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Charleroi
country: Belgium
facility: GHDC (Grand Hopital de Charleroi)
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: La Louviere
country: Belgium
facility: Centres Hospitaliers Jolimont
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Roeselare
country: Belgium
facility: AZ Delta Roeselare
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen - Sint-Augustinus
city: Woluwe-Saint-Lambert
country: Belgium
facility: Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: Universitaetsklinikum St. Josef-Hospital Bochum
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Med. Klinik u. Poliklinik I
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
city: Halle
country: Germany
facility: Studiengesellschaft BSF
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Hämatologisch-Onkologische Praxis Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: National Center for Tumor Diseases (NCT) Heidelberg
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel gGmbH
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
city: Marburg
country: Germany
facility: Klinikum der Philipps-Universität Marburg
city: München
country: Germany
facility: LMU Klinikum (Campus Großhadern) Medizinische Klinik Universität München
city: München
country: Germany
facility: Städtisches Klinikum München GmbH, Klinikum Neuperlach
city: Oldenburg In Holstein
country: Germany
facility: OhO Ostholstein Onkologie
city: Recklinghausen
country: Germany
facility: Prosper Hospital
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus - Centrum fuer Tumorerkrankungen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Avila
country: Spain
facility: Hospital Nuestra Senora de Sonsoles
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias - ICO Badalona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Clinic Hematolo/Oncologia- ICMHO, Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Universidad Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HMN Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
city: Málaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya Malaga - Instituto de Investigacion Biomedica de Malaga
city: Orense
country: Spain
facility: Complejo Hospitalario de Orense
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra (CHN)
city: Santander
country: Spain
facility: Hospital Universitario Marques De Valdecilla
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario De Santiago De Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - Hospital de la Mujer
city: Valencia
country: Spain
facility: Consorcio Hospital General Valencia
city: Vigo
country: Spain
facility: Complexo Hospitalario Universitario de Vigo (CHUVI)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Lund
country: Sweden
facility: Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)
city: Stockholm
country: Sweden
facility: Sodersjukhuset, Onkologiska Kliniken
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham-University Hospitals Birmingham NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust, Velindre Cancer Centre
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre - Gartnavel Royal Hospital - NHS Greater Glasgow and Clyde
city: London
country: United Kingdom
facility: St Bartholomew's Hospital-Barts Health NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust- Chelsea
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Torquay
country: United Kingdom
facility: Torbay Hospital - South Devon Healthcare Nhs Foundation Trust, Lowes Bridge
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: