Modi-1 Moditope in Breast, Head and Neck, Ovarian, or Renal Cancer

Exclusion Criteria

• •5. Patient has recovered to Grade ≤1 (CTCAE v5.0) from the effects (excluding alopecia) of any prior therapy for their malignancies.
• •6. Patient has at least one measurable lesion per RECIST 1.1 criteria by computed tomography (CT) scan or magnetic resonance imaging (MRI) (non-neoadjuvant cohorts).
• •7. Wherever possible, patients not scheduled for curative intent resection surgery should have a fresh tumour biopsy (or have an archival biopsy \[obtained within the past 5 years\] if obtaining a fresh biopsy is not feasible) at baseline for molecular studies, and agree to a post-treatment biopsy (at Week 25 or one of the EOT visits), if feasible. Patients in the SCCHN neoadjuvant cohort must have both a fresh pre-treatment biopsy and agree to have their resected tumour analysed.
• •8. Patient is male or female and at least 18 years of age.
• •9. Patient has a life expectancy of more than 6 months.
• •10. Patient has an ECOG performance status of 0 or 1.
• •11. Patient has adequate organ function as determined by the following laboratory values: absolute neutrophil count ≥1.5 x 109/L, platelets ≥100 x 109/L, haemoglobin \>90 g/L (\>5.6 mmol/L), lymphocytes ≥ 1 x 109/L, serum creatinine ≤1.5 x upper limit of the normal range (ULN), serum total bilirubin ≤1.5 x ULN, serum transaminases (aspartate aminotransferase \[AST\]/alanine aminotransferase \[ALT\]) ≤2.5 x ULN or ≤5.0 x ULN if liver metastases present.
• •12. Patient must be able and willing to provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or if a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed).
• •13. Women of child-bearing potential must have a negative serum pregnancy test during Screening (and a urine test within the 7 days prior to Day 1) and be neither breastfeeding nor intending to become pregnant during study participation. Women of child-bearing potential must agree to use highly effective contraceptive methods prior to study entry, for the duration of study participation, and for 120 days after discontinuation of vaccine monotherapy or 5 months after use with a CPI (or longer if the Summary of Product Characteristics \[SmPC\] of the CPI requires it).
• •14. Men who are potentially fertile with partners of child-bearing potential must agree to use highly effective contraceptive methods for the duration of study participation, and for 120 days after discontinuation of vaccine monotherapy or 5 months after use with a CPI (or longer if the SmPC of the CPI requires it).
• •15. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• •16. Patient scheduled to receive a CPI (e.g., pembrolizumab alone or nivolumab alone or where applicable with ipilimumab) together with Modi-1ev/Modi-1eKv must have been clinically evaluated, have not received prior CPI therapy, and the CPI must be deemed an appropriate treatment for their disease according to the CPI's SmPC (this does not apply to the neoadjuvant SCCHN cohort).
• •1. Patient has symptomatic central nervous system metastases or carcinomatous meningitis.
• •2. Patient is taking any systemic steroid therapy (exceeding 10 mg/day of prednisolone or equivalent) or is on any other form of immune suppressant medication within 2 weeks prior to the first dose of IMP. Physiological doses of systemic steroids such as those for the management of adrenal insufficiency, topical and inhaled steroids, such as those for the management of asthma, and patients with hypothyroidism stable on hormone replacement, are permitted.
• •3. Patient has a history of malignancy other than the disease under study within 2 years prior to Screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 2-year overall survival rate \>90%), such as adequately treated carcinoma-in-situ of the breast or the cervix, melanoma-in-situ, non-melanoma skin carcinoma, superficial bladder cancer, prostate cancer with Gleason grade ≤6 and prostate specific antigen within normal range or stage I endometrial cancer.
• •4. Patient is pregnant, lactating, or is expecting to conceive/father children within the duration of the study.
• •5. Patient has a concurrent illness which would preclude study conduct and assessment, including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection (considered opportunistic, life threatening, or clinically significant), uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease (including obstructive pulmonary disease and pulmonary fibrosis), alcoholic liver disease, or primary biliary cirrhosis.
• •6. Patient has New York Heart Association (NYHA) class III or IV heart disease, myocardial infarction or stroke within previous 6 months, a history of significant cardiac abnormality and/or significant abnormal baseline ECG readout, active ischaemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy, uncontrolled hypertension, significant cerebrovascular disease, or congestive heart failure.
• •7. Patient has anti-CCP antibody levels classified as equivocal or positive according to NHS guidelines, i.e., ≥ the ULN, or has an active autoimmune disease that may impact on the study treatment in the opinion of the Investigator.
• •8. Patient has received a live vaccine within 28 days, or an influenza vaccine within 14 days prior to the first dose of IMP. The timing of any other vaccines should be assessed on a case-by-case basis by the Investigator prior to study enrolment.
• •9. Patient has a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV; surface antigen reactive) or hepatitis C (HCV; RNA detected).
• •10. COVID-19 vaccination within 14 days prior to the first dose of IMP.
• •11. Patient has a known current or recent history (within the last year) of substance abuse including illicit drugs or alcohol.
• •12. History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR; including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis \[SJS/TEN\], or drug reaction with eosinophilia and systemic symptoms \[DRESS\]), or dose-limiting immune-mediated reactions (Modi-1ev/Modi-1eKv + CPI RCC cohort only).
• •13. Patient has a known hypersensitivity to the IMP under study or their excipients. Where SOC CPIs are planned to be given with the IMP, the patient must not have a known hypersensitivity to the CPIs or their excipients.