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

BioNTech

Status and phase: Enrolling; Phase 2

Conditions: Colorectal Cancer Stage III; Colorectal Cancer Stage II

Treatments: Drug: RO7198457 intravenous (IV); Other: Observational group (no intervention)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04486378

BNT122-01

2020-000451-12 (EudraCT Number)

U1111-1250-5294 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 229 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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229 participants in 4 patient groups

RO7198457

Experimental group

Description:

Participants will receive a recommended dose of RO7198457.

Treatment:

Drug: RO7198457 intravenous (IV)

Observational Group

Other group

Description:

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

Treatment:

Other: Observational group (no intervention)

Biomarker Cohort

Experimental group

Treatment:

Drug: RO7198457 intravenous (IV)

Exploratory Cohort

Experimental group

Treatment:

Drug: RO7198457 intravenous (IV)