PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO)

This is a Phase I/II, open-label, single-arm, multicenter study to evaluate the safety,
tolerability, immunogenicity and efficacy of a multiple subcutaneous injection of
PolyPEPI1018 as an add-on immunotherapy to the standard-of-care maintenance therapy in
approximately 15 subjects with metastatic colorectal cancer.

The first part of the study investigates the administration of a single vaccine dose during
12‑week follow‑up period on an outpatient basis. Screening is performed in parallel with the
subject's completion of the standard-of-care first-line treatment and initiation of the
standard-of-care maintenance treatment. A single dose of PolyPEPI1018 is administered after
the subject initiates the maintenance regimen, and within 3 weeks after the eligibility CT
scan was performed. Subjects are monitored every 3 weeks for 12 weeks.

The second part of the study investigates the administration of 3 vaccine doses (Weeks 0, 13,
26) then 12 weeks follow‑up on an outpatient basis.

Inclusion Criteria:

1. 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 originating from the colon or the
rectum

3. Presence of at least 1 measurable reference lesion according to the Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

4. Experienced PR or stable disease during first‑line treatment with a systemic
chemotherapy regimen and 1 biological therapy 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 drug

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. Eastern Cooperative Oncology Group (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 × 109/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

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 resolved, except for
oxaliplatin-related neuropathy or alopecia

17. Anticipated life expectancy ≥6 months Subject is willing and able to comply with the
requirements of the protocol

Exclusion Criteria:

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 high microsatellite instability (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

16. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated
drainage more than once every 28 days

17. Participants with active malignancy (other than colorectal cancer) 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 Absent or limited legal competence