CD8 PET Imaging in Metastatic Solid Tumours

Inclusion Criteria:

1. Age ≥ 18 years at the time of signing informed consent.

2. Patients with histologically confirmed diagnosis of locally advanced or metastaticsolid cancer types who, according to the opinion of the principal investigator,based on available clinical data, may benefit from anti-PD1 antibody therapy.

3. Disease progression following first-line therapy or any subsequent treatment line orno superior standard line of therapy available.

4. At least 1 lesion that is accessible per investigator's assessment and eligible forbiopsy according to standard clinical care procedures.

5. Measurable disease, as defined by standard RECIST v1.1. Previously irradiatedlesions should not be counted as target lesions except for lesions that haveprogressed after radiotherapy administered at least 3 months earlier.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. Life expectancy ≥ 12 weeks.

8. Adequate organ and bone marrow function as defined below:

9. Hemoglobin ≥9.0 g/dL

10. Absolute neutrophil count ≥1.0 x 109/L

11. Absolute lymphocyte count ≥0.75 x 109/L

12. Platelet count ≥75 x 109/L

13. Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated glomerularfiltration rate > 30 mL/min/1.73 m2. A 24-hour urine creatinine collection maysubstitute for the calculated creatinine clearance to meet eligibilitycriteria.

14. Adequate hepatic function: i. Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumour involvement); Patients withGilbert's syndrome do not need to meet total bilirubin requirements, provided theirtotal bilirubin is unchanged from their baseline. Gilbert's syndrome must bedocumented appropriately as past medical history. ii. Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumourinvolvement) iii. Alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if livertumour involvement) iv. Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver orbone tumour involvement)

15. Signed informed consent.

16. Willingness and ability to comply with all protocol required procedures.

17. For female patients of childbearing potential and male patients with partners ofchildbearing potential, agreement (by patient and/or partner) to use a highlyeffective form(s) of contraception (i.e., one that results in a low failure rate (< 1% per year) when used consistently and correctly)).

Exclusion Criteria:

1. Treatment with any approved anti-cancer therapy, investigational agent orparticipation in another clinical trial with therapeutic intent within 28 days priorto 89Zr-Df-crefmirlimab infusion and nivolumab or cetrelimab treatment.

2. Symptomatic, untreated brain metastasis, leptomeningeal disease, or spinal cordcompression. Patients are eligible if central nervous system (CNS) metastases areadequately treated and neurologically stable for at least 2 weeks prior toenrollment.

3. Prior ICI treatment, including but not limited to anti-PD1, anti-PD-L1 andanti-CTLA4 therapeutic antibodies.

4. Major surgical procedure other than for diagnosis within 28 days prior to 89Zr-Df-crefmirlimab infusion or anticipation of need for a major surgical procedureduring the course of the study.

5. History of autoimmune disease, including but not limited to myasthenia gravis,myositis, autoimmune hepatitis, systemic lupus erythematous, rheumatoid arthritis,inflammatory bowel disease, vascular thrombosis associated with antiphospholipidsyndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,multiple sclerosis, vasculitis or glomerulonephritis.

• Patients with a history of autoimmune-related hypothyroidism on a stable doseof thyroid replacement hormone may be eligible for his study.

• Patients with controlled type I diabetes mellitus on a stable dose of insulinregimen may be eligible for this study.

6. Treatment with systemic immunosuppressive medications (including but not limited toprednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, andanti-tumour necrosis factor agents) within 4 weeks prior to 89Zr-Df-crefmirlimabinfusion.

• Patients who have received acute, low-dose, systemic immunosuppressantmedications (e.g. a one-time of dexamethasone for nausea) may be enrolled inthe study after discussion with and approval by the sponsor.

• The use of inhaled corticosteroids for chronic obstructive pulmonary disease,mineralocorticoids (e.g. fludrocortisone) for patients with orthostatichypotension, and low-dose supplemental corticosteroids for adrenocorticalinsufficiency are allowed.

7. Prior allogeneic bone marrow transplantation or solid organ transplant.

8. Active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis Cor tuberculosis infection; or diagnosis of immunodeficiency.

• Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV)at screening.

• Patients with known HIV infection who have controlled infection (undetectableviral load (HIV ribonucleic acid (RNA) polymerase chain reaction (PCR)) and CD4count above 350 either spontaneously or on a stable antiviral regimen arepermitted. For patients with controlled HIV infection, monitoring will beperformed per local standards.

• Patients with hepatitis B who have a controlled infection (serum HBVdeoxyribonucleic acid (DNA) PCR that is below the limit of detection ANDreceiving anti-viral therapy for hepatitis B) are permitted. Patients withcontrolled infections must undergo periodic monitoring of HBV DNA. Patientsmust remain on anti-viral therapy for at least 6 months beyond the last dose ofinvestigational study drug.

• Patients who are HCV antibody positive who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to asuccessful prior course of anti-HCV therapy) are permitted.

• Patients positive for HCV antibody are eligible only if PCR is negative for HCVRNA.

9. Receipt of a live vaccine (including attenuated) within 30 days of planned start ofstudy medication.

10. Evidence of an active infection that requires systemic antibiotics within 2 weeksprior to 89Zr-Df-crefmirlimab infusion.

11. At least 2 weeks recovered from COVID 19 infection, where this infection has to bedocumented in the case record form.

12. Any other diseases, metabolic dysfunction, physical examination finding, or clinicallaboratory finding giving reasonable suspicion of a disease or condition thatcontraindicates the use of 89Zr-Df-crefmirlimab, or that may affect theinterpretation of the results or render the patient at high risk from complications.

13. Altered mental status, or any psychiatric condition that would prohibit theunderstanding or rendering of informed consent.

14. Sponsor employee/member of the clinical site study team and/or his or her immediatefamily

15. Women with a positive serum chorionic gonadotropin HCG pregnancy test at thescreening/baseline visit. Breastfeeding women are also excluded.

16. Women of childbearing potential* and sexually active men who are unwilling topractice highly effective contraception prior to the first dose of study therapy,during the study, and for at least 6 months after the last dose. Highly effectivecontraceptive measures include:

• stable use of combined (estrogen and progestogen containing) hormonalcontraception (oral, intravaginal, transdermal) or progestogen-only hormonalcontraception (oral, injectable, implantable) associated with inhibition ofovulation initiated 2 or more menstrual cycles prior to screening

• intrauterine device (IUD); intrauterine hormone-releasing system (IUS)

• bilateral tubal ligation

• vasectomized partner (provided that the male vasectomized partner is the solesexual partner of the women of childbearing potential (WOCBP) study participantand that the vasectomized partner has obtained medical assessment of surgicalsuccess for the procedure)

• and/or sexual abstinence.

17. Contraindications for MRI scan

18. Patients who have any splenic disorders, or had splenectomy, that could compromiseprotocol objectives