BNT122-01

1. Patients must be a man or woman of at least 18 years of age.

2. Patients must have given informed consent indicating that they understand the purpose of and procedures required for the trial and are willing to participate in the trial.

3. Patients must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III colon cancer per AJCC 2017 that has been surgically totally resected (R0 confirmed by pathology report). Stage II (high risk) colon cancer is defined by the NCCN Guidelines® for Colon Cancer V.2.2020 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.

4. Patients must have detectable ctDNA prior to start of AdCTx (except for the Biomarker Cohort), detected with the Avenio Oncology Assay (AOA) Surveillance Test.

· ctDNA assay must be performed through this study or study BNT000-001 ctDNA screening protocol.

5. Patients must have an ECOG Performance Status of 0-1.

6. Patients must have organ and bone marrow function, in line with all of the following:

· ANC ³ 1.5 ´ 109/L (1500/mL) without granulocyte colony-stimulating factor support.

· Lymphocyte count ³ 0.5 ´ 109/L (500/mL).

· Platelet count ³ 100 ´ 109/L (100,000/μL) without transfusion.

· Hemoglobin ³ 90 g/L (9 g/dL) patients may be transfused to meet this criterion.

· For patients not receiving therapeutic anticoagulation: INR or aPTT

£ 1.5 ´ upper limit of normal (ULN).

· For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.

· GFR ³ 30 mL/min.

· AST, ALT, and ALP £ 2.5 ´ ULN.

· Bilirubin £ 1.5 ´ ULN with the following exception: for patients with known Gilbert disease: bilirubin £ 3 ´ ULN.

7. Women must be either:

· Not of childbearing potential as defined in Section 10.4.

OR

· If of childbearing potential, be practicing a highly effective method of birth control during the trial and for 28 d after receiving the last dose of RO7198457 as defined in Section 10.4.

8. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test.

9. Men who are sexually active with women of childbearing potential and who have not had a vasectomy must agree to use a highly effective method of birth control (as defined in Section 10.4) during the trial and for 28 d after receiving the last dose of IMP.

10. Patients must be willing and able to adhere to the restrictions specified in this protocol.

11. Adequate tumor material in formalin-fixed paraffin embedded (FFPE) blocks or as sectioned tissue (only upon approval by sponsor) must be available (as described in the Laboratory Manual). Resections are preferred. The specimens should be submitted along with an associated pathology report. Multiple samples may be provided for a given patient, on the basis of availability; however, the requirement for a block or sectioned tissue should be satisfied by a single specimen. Priority should be given to the tissue with

the highest tumor content and lowest necrotic area.

12. At least 5 tumor neoantigens identified in the provided tumor sample.

13. The patient has started a standard of care AdCTx within 8 wks post-surgery and has completed at least 3 mon of treatment of a 3 or a 6 mon course of chemotherapy. 

1. Patients with uncontrolled intercurrent illness, including any of but not limited to:

· Severe infections within 4 wks prior to the first dose of RO7198457 including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.

· Symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.

· Respiratory failure.

· Recent infections not meeting the criteria for severe infections, including the following:

- Signs or symptoms of infection within 2 wks prior to the first dose of RO7198457

- Received oral or IV antibiotics within 2 wks prior to the first dose of RO7198457

- Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.

2. Diagnosed MSI high tumors.

3. Prior therapy with any of the following:

· Neo-adjuvant (radio)chemotherapy prior to surgery.

· Treatment with systemic immunosuppressive medication within 2 wks 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 d prior to randomization) treatment with another investigational drug.

4. 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.

5. Patients who developed metastatic disease during screening/receiving standard of care treatment (not applicable for Exploratory Cohort).

6. 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 PSA level < 0.1 ng/mL.

· Any curable cancer with a complete response (CR) of > 2 years duration.

7. Patients with known allergies, hypersensitivity, or intolerance to RO7198457 or its excipients.

8. Patients are currently enrolled in an ongoing clinical trial or trial that could interfere with the protocol-specified assessments.

9. Patients with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the patients well-being) or that could prevent, limit, or confound the protocolspecified assessments.

10. Patients who had major surgery (e.g., surgery requiring general anesthesia) within 4 wks 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.

11. 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).

12. Active Hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.

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

14. Patients who were enrolled in this trial before.

15. Patients who are breastfeeding at screening visits 2 or 3, or who plan to breastfeed during the trial, starting after the start of treatment with RO7198457 and continuously until at least 90 d after receiving the last dose of RO7198457. 

Lead Research Nurse: Rashmi Madan (x2136) Rashmi.Madan@LTHTR.nhs.uk

Clinical Trials Administrator : Yecora Lecanda-Swarbrick (x3766)