A two-part, open-label, clinical study to assess the safety, tolerability and activity of intravenous doses of ICT01 in combination with low-dose subcutaneous interleukin-2 in patients with advanced solid tumors (EVICTION-2)

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• Any malignancy of γ9δ2 T cell origin 2) Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment 3) Treatment with investigational drugs within 28 days, or 5 half-lives, whichever is longer, before study treatment 4) Systemic steroids at a daily dose of >10 mg of prednisone, >2 mg of dexamethasone or equivalent, for the last 28 days and ongoing 5) Patients with rapidly progressing disease defined as advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term (e.g., during Screening Period/ treatment washout) that includes patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement 6) Ongoing immune-related adverse events ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy. 7) Ongoing systemic autoimmune disease requiring systemic immunosuppressive therapy 8) Primary or secondary immune deficiency 9) Active and uncontrolled infections requiring IV antibiotic or antiviral treatment 10) Known/suspected hypersensitivity against ICT01, human or humanized IgGs, IL-2 (Proleukin®), pembrolizumabor their excipients 11) Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) 12) Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year before study entry 13) Dementia or altered mental status that would prohibit informed consent 14) Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator 15) Active drug or alcohol abuse as assessed by the Investigator 16) Patients with uncontrolled and symptomatic brain metastases or seizure disorders. Patient with asymptomatic brain metastases are allowed provided they are stable and off therapeutic steroids for at least 4 weeks 17) Patients who have received vaccination with a live-attenuated vaccine within 30 days prior to study treatment initiation 18) Patients with contraindications to IL-2 according to the Summary of Product Characteristics (SmPC), including organ allografts and pre-existing severe major organ dysfunction. 19) For cohorts 13, 14 and 15 in combination with Pembrolizumab: patients with prior allogeneic HSCT or solid organ transplant

• Male or female aged ≥18 years 2) Voluntarily signed written informed consent before performance of any study-related screening procedures 3) Relapsed/refractory patients who have failed at least 2 lines of systemic therapy or who failed first line therapy and are intolerant of or have a contraindication to the standard second line of therapy with histologically or cytologically confirmed diagnosis of: a. metastatic colorectal cancer (mCRC)i. patients must have progressed after receiving a fluoropyrimidine, oxaliplatin, and irinotecan and an antiangiogenic agent ii. patients with tumors known to be microsatellite instability-high (MSI-H), prior therapy with a checkpoint inhibitor is required if they were clinically able to receive it iii. patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type should have received anti-EGFR therapy. b. metastatic ovarian cancer: i. patients must be platinum resistant and must have had at least one treatment line after being resistant to platinum-based chemotherapy c. metastatic castration-resistant prostate cancer (mCRPC) d. metastatic pancreatic ductal adenocarcinoma (PDAC) e. metastatic or unresectable refractory melanoma with primary resistance following at least 6 weeks of prior CPI treatment, defined as best response of progressive disease or SD of short duration (lasting less than 6 months), as per Society for Immunotherapy of Cancer [SITC] Immunotherapy Resistance Taskforce [Kluger et al 2020]). Patients must have no available standard of care or treatment with potential survival benefit for their disease, as determined by the treating Investigator. Melanoma patients who have proto-oncogene B Raf (BRAF) V600E or V600K mutations must have received prior combination BRAF and mitogen-activated protein kinase (MEK) inhibitor therapy unless they have contraindications, as determined by the treating Investigator. 4) Availability of baseline tumor biopsy and willingness to undergo on-study tumor biopsies5) Eastern Cooperative Oncology Group (ECOG) performance status ≤1 6) Life expectancy >3 months as assessed by the Investigator 7) Clinical laboratory assessments: a. Hematology: - Hemoglobin ≥8.5 g/dL (equal to 5.28 mmol/L; transfusion dependent or independent); - platelet count ≥100 × 109/L; - lymphocyte count ≥0.5 × 109/L; - absolute neutrophil count ≥1.0 × 109/L; - White Blood Count (WBC) ≥4 × 109/L b. Liver enzymes: - aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN) (<5 × ULN in the case of liver metastases);- bilirubin ≤1.5 × ULN (<2 × ULN in case of liver metastases); c. Renal function: serum creatinine <1.5 × ULN or creatinine clearance ≥50 mL/min (Cockcroft and Gault) for serum creatinine ≥1.5x ULN. 8) Pulse oximetry of 95% or higher at rest, unless patient has chronic lung disease where 90% or higher at rest is acceptable 9) Contraceptives measures10) Women must not be breastfeeding 11) At least 1 measurable lesion per RECIST