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

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

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.

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

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.