START: Safety and Anti-Tumor Activity of PeptiCRAd-1 in Treatment of Cancer

Inclusion Criteria:

1. Written informed consent.

2. Male or female, ≥18 years of age.

3. Patients with any 1 of the following histologically confirmed tumors and whoqualifies for new or continued CPI therapy and relapsing to/after standard therapyor the patient has refused or does not tolerate standard therapy:

• Inoperable/metastatic cutaneous malignant melanoma

• Relapsed or newly diagnosed locally advanced inoperable/metastatic TNBC

• Inoperable advanced/metastatic non-squamous NSCLC

• Inoperable and/or advanced Synovial or myxoid round cell sarcoma

• Inoperable and/or advanced osteosarcoma

• Inoperable and/or advanced colorectal cancer, patients assessed as positive forNY-ESO-1 or MAGE-A3 expression at baseline

• Inoperable and/or advanced/metastatic sarcoma, patients assessed as positivefor NY-ESO-1 or MAGE-A3 expression at baseline

4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

5. Tumor lesion which is deemed feasible for biopsy and injection

6. ECOG/WHO performance status 0 to 1.

7. Acceptable liver and renal function, defined as:

• Total bilirubin ≤1.5 x upper limit of normal (ULN; does not include patientswith Gilbert's Disease), and

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN,and

• Serum creatinine ≤1.5 x ULN

8. Acceptable hematological function, defined as:

• Hemoglobin ≥9 g/dL, and

• Neutrophils ≥1.5 x 109/L, and

• Platelet count ≥100 x 109/L Patients may be transfused to meet the hemoglobinentry criteria.

9. Acceptable coagulation status defined by international normalized ratio (INR) ofblood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal.

10. Negative pregnancy test at screening in all women of childbearing potential (WOCBP).Such patients must agree to use a highly effective method of contraception (Appendix

1. during study intervention and for 3 months after the last virus treatment, 4months after the last dose of pembrolizumab, and 12 months after CPO dosing. Malepatients and male partners of female patients must also use barrier contraception,i.e., condom, for the time periods specified for WOCBP, plus a further 3 monthperiod. Urine pregnancy tests should have a sensitivity of at least 25 mIU/mL for humanchorionic gonadotropin (hCG). If the urine test is positive, it must be followed bya quantitative analysis of hCG concentration in blood.

11. Prior therapy with an immune CPI is allowed provided a 6-week washout period isobserved for patients with prior programmed cell death (PD)1 or PDL1 treatment

Exclusion Criteria:

1. Receipt of any oncolytic virus treatment, or administration of a vaccine containinglive virus within 4 weeks before Day 1.

2. Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1.Inhaled or topical corticosteroid use is allowed.

3. Prior or concomitant radiotherapy within 4 weeks before Day 1.

4. Participation in a study with an investigational drug or device within 4 weeks priorto Day 1.

5. Active bacterial, viral, or fungal infection that requires systemic therapy.

6. Active autoimmune disease that has required systemic treatment in the past twoyears.

7. Concomitant disease or condition that could interfere with the conduct of the study,or that would, in the opinion of the investigator, pose an unacceptable risk to thepatient, if included in this study.

8. Any concomitant medical condition requiring receipt of a therapeutic anticoagulantthat, in the opinion of the treating physician, cannot safely be withheld to allowfor repeated injection of PeptiCRAd 1 and tumor biopsies.

9. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C oractive tuberculosis.

10. Known active central nervous system metastases. Patients with leptomeningealdisease, carcinomatous meningitis, symptomatic brain metastases, or radiographicsigns of CNS hemorrhage are excluded. Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids andanticonvulsants for at least 7 days) are permitted.

11. Any prior severe AE according to Common Terminology Criteria for Adverse Events (CTCAE), severe hypersensitivity reaction attributed to prior anti-PD1 or PDL1therapy or components of the study intervention or has a history of anycontraindication that, in the investigator's opinion, would contraindicatepembrolizumab administration such as:

• Resolution of side effect of prior anti-PD1 or PDL1 therapy to Grade 1

• Grade 2 or higher pneumonitis

• Grade 4 AST or ALT elevation

• Grade 3 or higher colitis attributable to immunotherapy Note: in the absence ofclinical symptoms of pancreatitis, elevations of amylase or lipase are notcontraindications to therapy on this trial.

12. History of or planned tissue / organ transplant.

13. Females who are pregnant or breast feeding or expecting to conceive within theprojected duration of the study starting with the screening visit or males expectingto father children within the projected duration of the study starting with thescreening visit.

14. Unwillingness or inability to comply with the study protocol for any reason.

15. Admission to an institution by virtue of an order issued by the judicial oradministrative authorities.

16. Sponsor or Contract Research Organization employees, or employees under the directsupervision of the investigator or the investigational sites and/or involveddirectly in the study.

17. Prior or concurrent malignancy, unless the natural history or treatment of thedisease does not have the potential to interfere with the safety or efficacyassessment of the investigational regimen.