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

• ClinicalTrials.gov Identifier: NCT04486378
• Recruitment Status: Recruiting
• First Posted: July 24, 2020
• Last Update Posted: May 8, 2024
• Sponsor: BioNTech SE
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: July 20, 2020
• First Posted Date: July 24, 2020
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: March 8, 2021
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2020)

Disease-free survival (DFS) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 22, 2024)

• Relapse-free survival (RFS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Through study completion, up to 5 years ]
  OS defined as the time from randomization to death from any cause.
• Change of ctDNA status (approximately every 3 months) [ Time Frame: Through study completion, up to 5 years ]
• Occurrence of treatment emergent adverse event (TEAE) [ Time Frame: 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. [ Time Frame: 15 months ]

Original Secondary Outcome Measures (submitted: July 20, 2020)

• Relapse-free survival (RFS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
  • Loss to follow-up and non-cancer-related deaths are censored.
• Overall survival (OS) [ Time Frame: Through study completion, up to 5 years ]
  OS defined as the time from randomization to death from any cause.
• Change of Circulating tumor DNA (ctDNA) status (every 3 months) [ Time Frame: Through study completion, up to 5 years ]
• Occurrence of treatment emergent adverse event (TEAE) [ Time Frame: 15 months ]
  TEAE, including Grade 3+, serious, fatal TEAE by relationship (AEs graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events, version 5.0 [CTCAE v5.0])
• Occurrence of dose reduction and discontinuation of IMP due to a TEAE. [ Time Frame: 15 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer Stage II
• Colorectal Cancer Stage III

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

Study Arms

• Experimental: RO7198457
  Participants will receive a recommended dose of RO7198457.
  Intervention: Drug: RO7198457 intravenous (IV)
• Observational Group
  Observational group will undergo watchful waiting, which is the standard of care in this setting.
  Intervention: Other: Observational group (no intervention)
• Experimental: Biomarker Cohort
  15 patients
  Intervention: Drug: RO7198457 intravenous (IV)
• Experimental: Exploratory Cohort
  20 patients
  Intervention: Drug: RO7198457 intravenous (IV)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 22, 2024): 229
• Original Estimated Enrollment (submitted: July 20, 2020): 201
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

• Listed Location Countries: Belgium, Germany, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT04486378
• Other Study ID Numbers: BNT122-01; 2020-000451-12 ( EudraCT Number ); U1111-1250-5294 ( Other Identifier: WHO Universal Trial Number (UTN) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: BioNTech RNA Pharmaceuticals GmbH
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: BioNTech RNA Pharmaceuticals GmbH
• Collaborators: Genentech, Inc.

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

• PRS Account: BioNTech SE
• Verification Date: May 2024