Male or female subjects, 18 -75 years of age at time of Screening who provide written informed consent prior to initiation of any study procedure 2. Histologically confirmed metastatic adenocarcinoma ori ginating from the colon or the rectum 3. Presence of at least 1 measurable reference lesion according to the RECIST version 1.1 criteria 4. Experienced PR or stable disease during first -line treatment with a systemic chemotherapy regimen and 1 biological therap y regimen 5. Maintenance therapy with a fluoropyrimidine (5-fluorouracil or capecitabine) plus the same biologic agent (bevacizumab, cetuximab or panitumumab) used during induction, scheduled to initiate prior to the first day of treatment with the study dru g 6. No more than 1 line of chemotherapy regimen for mCRC (adjuvant therapy for non-metastasized disease is allowed if terminated more than 6 months before Screening and without recurrence within 6 months after the end of adjuvant treatment) 7. Last CT scan at 3 weeks or less before the first day of treatment 8. ECOG performance status of 0 or 1 9. Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of <1% per year) for 3 months from the day of the treatment. An effective form of contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, cervical cap or condom 10. Men must agree to use an effective form of contraception (as defined above), and not donate sperm for 3 months from the day of the treatment 11. White blood cell count ≥3.0 × 10 9/L with neutrophils ≥1.5 × 109/L 12. Platelets ≥100 × 109/L, hemoglobin ≥5.6 mmol/L (corresponding to 9 g/dL) 13. Serum bilirubin ≤1.5 × upper limit of normal (ULN) set by the site Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 35 of 81 CONFIDENTIAL 14. Alanine amino transferase (ALAT) and aspartate amino transferase (ASAT) ≤2.5 × ULN in the absence of liver metastases. ALAT and ASAT ≤5 × ULN set by the site in the presence of liver metastases 15. Serum creatinine ≤ 1.5 × ULN set by the site and creatinine clearance >30 mL/min using Cockroft formula 16. Relevant toxicities of prior therapies must have r esolved, except for oxaliplatin -related neuropathy or alopecia 17. Anticipated life expectancy ≥6 months 18. Subject is willing a nd able to comply with the requirements of the protocol 4.2 Exclusion Criteria Subjects who meet ANY of the following criteria are not eligible for this study: 1. Received chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks prior to start of study treatment 2. Received continuous systemic steroid treatment within the last 2 weeks prior to start of study treatment 3. Colorectal cancer with documented MSI -H 4. Colorectal cancer with documented BRAF mutations 5. Pre-existing systemic autoimmune or antibody -mediated diseases or immune deficiency diseases 6. Central nervous system (CNS) metastases 7. Active or uncontrolled severe infections or undiagnosed febrile condition >38ºC 8. Acute or subacute intestinal obstruction or history of chronic intestinal inflammatory diseases 9. Symptomatic peritoneal carcinomatosis 10. Peritonitis 11. Serious, non-healing wounds, ulcers or bone fractures 12. Nephrotic syndrome 13. Arterial thromboembolisms or severe hemorrhages within 6 months before study enrolment (except bleeding tumor before tumor resection surgery) 14. Hemorrhagic diathesis or thrombotic tendency 15. Major surgery or radiotherapy within 12 weeks prior to the study treatment or anticipation of needing such procedure during the study period Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 36 of 81 CONFIDENTIAL 16. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days 17. Participants with active malignancy (other than CRC) or a prior malignancy within the past 12 months 18. Participant with myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to the first dose of study treatment, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant 19. Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study 20. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study 21. Known hypersensitivity to any component of the investigational drug 22. If female, participant is pregnant (exclusion confirmed with beta-human chorionic gonadotropin [hCG] test) or lactating at the time of enrollment, or has plans to become pregnant or start breastfeeding during the study 23. Pre-existing alcohol or drug abuse 24. Medical or mental impairments which make it impossible to obtain the patient’s consent or to conduct the study 25. A significant concomitant medical condition which the clinical investigator believes precludes the patient from enrolling in the study 26. Absent or limited legal competence 4.3 Subject Withdrawal and Discontinuation Any subject may voluntarily withdraw consent (i.e., reduce the degree of participation in the study) for aspects of continued participation and data collection. The reason for withdrawal will be recorded on the End of Study Case Report Form ( CRF). Assessments to be performed at the Last Visit are described in Section 7.4. Discontinuation (i.e., complete withdrawal from study participation) may be due to dropout (i.e., active discontinuation by subject) or loss to follow-up (i.e., discontinuation by subject without notice or action). Additionally, the investigator and sponsor have the discretion to Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 37 of 81 CONFIDENTIAL discontinue any subject from the study if, in their judgment, continued participation would pose an unacceptable risk for the subject. During the initial study period, that is during the 12 weeks following the first vaccination, if a patient experiences disease progression and needs to start a second -line therapy, the patient will be withdrawn from the study. This is required to obtain a complete (12 weeks) measurement of the immunological response curve after the initial vaccination, that is one of the original study objectives. In contrast, if a patient experiences disease progressi on and needs to start a second -line therapy after the second vaccination , the patient will remain in the study, receive the third vaccination as scheduled and complete follow- up. This will allow to gain a better sense of initial efficacy of the PolyPEPI 1018 vaccine, that is another study objective. If a subject must be withdrawn from the study, the responsible designee medical monitor will be informed immediately, and this person will then notify the sponsor’s medically responsible party . All subjects who prematurely discontinue from the study, regardless of cause, should be seen as soon as possible and undergo the assessments specified for the Last Visit (see Section 7.4). If there is a medical reason for withdrawal, the subject will remain under the supervision of the investigator until satisfactory health has returned or health has stabilized. The investigator will inform the subject’s primary health care provider (as applicable) as agreed by the subject, to ensure the subject receives the appropriate follow- up and care. If the subject is prematurely discontinuing due to withdrawal of consent, the investigator should clarify the level of consent withdrawal with the subject (i.e., consent withdrawal with regard to permission to utilize samples already collected but not analyzed and willingness to return for safety follow -up assessments). The level of consent withdrawal should be document ed this in the electronic case report form (eCRF) For subjects who are lost to follow-up (i.e., those subjects whose status is unclear because they fail to appear for study visits without stating an intention to withdraw), the investigator Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 38 of 81 CONFIDENTIAL should show “due diligence” by documenting in the source documents all steps taken to contact the subject (e.g., dates of telephone calls and registered letters ). Subjects who discontinue or are withdrawn from the study , including withdrawal after receipt of the study’s IP on or after Day 1 of Week 0 , will be replaced, except for subject s who experience a DLT : a subject who experiences a DLT will be withdrawn from the study and will not be replac ed. 4.3.1 Permanent Treatment Discontinuation Subjects will be permanently withdrawn from treatment for the following reasons: • Vaccine-related toxicity ( Section 5.5) • Requirement of prohibited concomitant medications ( Section 5.4.2) • Request by subject to terminate study • Completion of the study treatment as defined by the protocol • Clinical reasons believed life threatening by the physician, even if not addressed in Section 5.5 4.3.2 Premature Treatment Discontinuation Subjects will be prematurely discontinued from treatment for the following reasons: • Failure by the subject to attend two consecutive clinic visits • Request by the subject to withdraw • Pregnancy • Development of an exclusionary condition as outlined in Section 4.2 • Request of the primary care provider if s/he thinks the study is no longer in the best interest of the subject • Subject judged by the investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results • Subject reaches a defined study endpoint, as outlined in Se ction 3.2, if applicable • At the discretion of the health authority , IRB/IEC, investigator, or pharmaceutical supporter Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 39 of 81 CONFIDENTIAL 5 STUDY TREATMENTS 5.1 PolyPEPI 1018 CRC Vaccine 5.1.1 Description 5.1.1.1 Vaccine Substance The vaccine is composed of 6 synthetic peptides and is manufactured according to Good Manufacturing Practices (GMP) using solid phase peptide synthesis. The vaccine substance should be stored in vials as a peptide solution (0.2 mg/ mL in DMSO/water) at -20ºC.