A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors

Inclusion Criteria:

• Participants with the following histologically or cytologically confirmed solidtumor indications and line of treatment:

1. Non-small cell lung cancer (NSCLC).

2. Colorectal cancer.

3. Cutaneous squamous cell carcinoma (cSCC).

4. Advanced hepatocellular carcinoma (not applicable in France).

5. mCRPC.

6. Ovarian cancer.

• Have measurable disease per RECIST 1.1. mCRPC participants with no measurabledisease and only widespread bone disease must have a CTC count of ≥5 cells per 7.5mL of blood.

• Availability of tumor tissue from a fresh biopsy at screening unless the biopsycannot be obtained due to safety reasons or non-accessibility of the tumor site. Ifit is not possible to obtain a fresh biopsy, every effort should be taken toretrieve an archival biopsy. Archived, fixed tumor tissue may only be collected iftaken preferentially after completion of the most recent systemic tumor therapy andwithin 12 months prior to the first dose of study treatment.

• Eastern Cooperative Oncology Group (ECOG) score 0-1.

• Have recovered from all AEs (except alopecia) due to previous therapies to grade ≤1 (excluding alopecia) or have stable grade 2 neuropathy.

• Have adequate organ function as defined below:

1. Hematology:

2. Absolute neutrophil count ≥1500/μL.

3. Platelets ≥100 000/μL.

4. Hemoglobin ≥9.0 g/dL .

5. Renal function: Creatinine clearance as measured by glomerular filtration rate ≥30 mL/min using Cockcroft-Gault equation.

6. Hepatic function: Alanine transaminase (ALT)/aspartate transaminase (AST) ≤2.5×upper limit of normal (ULN) and total bilirubin ≤1.5×ULN or direct bilirubin ≤ULN in participants without liver metastasis. In participants with livermetastasis, ALT/AST ≤5×ULN is allowed but total bilirubin must be ≤2×ULN.

7. Prothrombin time and activated partial thromboplastin time ≤1.5×ULN.

• Participants must not have active hepatitis B or hepatitis C infection.

• Adequate contraception must be applied in all women of childbearing potential (WOCBP) and in male participants.

Exclusion Criteria:

• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell deathligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory orco-inhibitory T-cell receptor and was discontinued from that treatment due to agrade ≥3 AE.

• Prior exposure to agonists of interleukin (IL)-2 or IL-15.

• Prior systemic anti-cancer therapies, including investigational agents:

1. Less than 4 weeks for systemic chemotherapy and immuno-oncology therapies; andfor tyrosine kinase inhibitors 4 weeks or 5 half-lives (whichever is shorter).

2. Less than 4 weeks from major surgeries and not recovered adequately.

• Has received prior radiotherapy within 2 weeks of the start of study interventionsor have had a history of radiation pneumonitis.

• NSCLC indication only: Received radiation therapy to the lung >30 Gy within 6months.

• Has received a live or live-attenuated vaccine within 30 days.

• Clinically significant cardiac abnormalities including prior history of any of thefollowing:

1. Cardiomyopathy, with left ventricular ejection fraction ≤ 50%.

2. Congestive heart failure of New York Heart Association grade ≥2.

3. History of clinically significant artery or coronary heart disease.

4. Prolongation of QTcF >450 msec .

5. Clinically significant cardiac arrythmia that cannot be controlled withadequate medication.

• Uncontrolled hypertension defined as systolic blood pressure >160 mmHg, diastolicblood pressure >110 mmHg.

• Prior allogeneic hematopoietic stem cell transplantation within the last 5 years.

• Prior allogeneic tissue/solid organ transplant.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy.

• History of or serology positive for human immunodeficiency virus (HIV).

• Has a known additional malignancy that is progressing or has required activetreatment within the past 5 years, except for basal cell carcinoma of the skin orcarcinoma in situ that have undergone potentially curative therapy are not excluded.

• Has known active central nervous system metastases and/or carcinomatous meningitis,unless stable.

• Had severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of itsexcipients.

• Has an active autoimmune disease that has required systemic treatment in the past 2years.

• History of (non-infectious) pneumonitis/interstitial lung disease that requiredsteroids or current pneumonitis/interstitial lung disease.

• Has an active infection requiring systemic therapy.

• Has any condition that might confound the results of the study or interfere with theparticipant's participation for the full duration of the study.