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

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)/StageIII colon cancer per American Joint Committee on Cancer (AJCC) 2017 that has beensurgically 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 factorsfor 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 6months of initial diagnosis) per AJCC 2017, after standard of care (SoC)primary resection and curative-intent hepatectomy (R0 confirmed bypathology report) with or without (neo-)adjuvant chemotherapy (prior tohepatectomy), and planned adjuvant chemotherapy.

• For the Biomarker Cohort: patients with tumors of the colon, including butnot limited to, colon adenocarcinoma, carcinoid tumors (including gobletcell carcinoid/adenocarcinoma), and tumors of the appendix, whose tumorswere surgically resected and are planned for adjuvant chemotherapy (perinstitutional 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 ctDNAscreening 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 definedby the protocol.

• Adequate tumor material in formalin-fixed paraffin embedded blocks or as sectionedtissue (only upon approval by sponsor) must be available (as described in thelaboratory manual). For the CLM Cohort: tumor material must come from primaryresection for patients who undergo staged approach, or from available archivalmaterial 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 nolater than 10 weeks post-surgery and has completed at least 3 months of treatment ofa 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 upto 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, afterhepatectomy. For the Biomarker Cohort: patient must have received at least one cycleof 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 toinitiation of trial treatment or anticipation of need for systemicimmunosuppressive medication during trial treatment, with the exception of lowdose steroids defined as 10 mg oral prednisone (or equivalent).

• Current or recent (within the 28 days prior to randomization) treatment withanother investigational drug.

• Exception for the CLM Cohort: primary tumor must be resected and (neo-)adjuvant chemotherapy prior to curative-intent hepatectomy isaccepted.

• Toxicities from previous anti-cancer therapies that have not resolved to baselinelevels or to Grade 1 or less except for alopecia and peripheral neuropathy.

• Patients who developed metastatic disease during screening/receiving standard ofcare 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 itsexcipients.

• Patients who had major surgery (e.g., surgery requiring general anesthesia) within 4weeks before screening, or will not have fully recovered from surgery, or havesurgery planned during the time the patient are expected to participate in thetrial.

• Patients with positive serology for hepatitis B indicative of active hepatitis Binfection:

• Positive test for hepatitis B surface antigen (HBsAg) OR

• Negative test for HBsAg AND positive test for antibodies to hepatitis B coreantigens (anti-HBc) AND positive test for hepatitis B virus (HBV) DNA.

• Serological markers indicative of vaccination (isolated antibodies tohepatitis B surface antigens [anti-HBs]) or resolved natural infectionwithout viral load (anti-HBc with negative HBsAg and negative HBV DNA) arenot exclusionary.

• Active Hepatitis C virus (HCV) infection; patients who have completed curativeantiviral treatment with HCV viral load below the limit of quantification areallowed.

• Patients who have a history of human immunodeficiency virus (HIV) antibodypositivity, or tests positive for HIV at screening.

• Patients who have had prior splenectomy.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.