Pazopanib With or Without Pembrolizumab for Metastatic Soft Tissue Sarcoma

Inclusion Criteria:

1. Histologically confirmed Soft Tissue Sarcoma(STS) progression to 1 or 2 (less than

3. prior chemotherapy

: Exclude pazopanib-resistant subtype - embryonal rhabdomyosarcoma, chondrosarcoma,osteosarcoma, Ewing tumours, primitive neuroectodermal tumour, gastrointestinalstromal tumour, dermatofibrosarcoma protuberans, inflammatory myofibroblasticsarcoma, and liposarcoma

2. Age > 19 years at time of study entry.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 7days before screening)

4. Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1

5. Adequate normal organ and marrow function as defined below

• Hemoglobin ≥9.0 g/dL

• Absolute neutrophil count (ANC) ≥ 1500 per mm3

• Platelet count ≥ 100,000 per mm3

• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).

• Aspartate Aminotransferase (AST, SGOT)/Alanine Aminotransferase (ALT, SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present,in which case it must be ≤5x ULN

• Creatinine≤1.5 x ULN or Measured or calculated(CrCl should be calculated perinstitutional standard) creatinine clearance(GFR can also be used in place ofcreatinine or CrCl) ≥ 1.5 x institutional ULN

• International normalized ratio (INR) OR prothrombin time (PT) and activatedpartial thromboplastin time (aPTT) : ≤1.5 × ULN unless participant is receivinganticoagulant therapy as long as PT or aPTT is within therapeutic range ofintended use of anticoagulants

6. The participant (or legally acceptable representative if applicable) provideswritten informed consent for the trial.

7. A male or female participant must agree to use a contraception as detailed inAppendix 2 of this protocol during the treatment period and for at least 120 daysafter the last dose of study treatment and refrain from donating sperm during thisperiod.

8. A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and at least one of the following conditions applies:

9. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR

10. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 duringthe treatment period and for at least 120 days after the last dose of studytreatment.

11. Archival tumor tissue sample or newly obtained [core, incisional or excisional]biopsy of a tumor lesion not previously irradiated has been provided.Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.Newly obtained biopsies are preferred to archived tissue.

Exclusion Criteria:

1. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,endocrine therapy, targeted therapy, biologic therapy, tumor embolization,monoclonal antibodies, other investigational agent) 28 days prior to the first doseof study drug

2. Any previous treatment with a Programmed Death-1(PD1) or ProgrammedDeath-Ligand1(PD-L1) inhibitor, anti-PD-L2 agent, stimulatory/co-inhibitory T-cellreceptor (eg. CTLA-4, OX-40, CD137), and/or pazopanib

3. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with theexception of alopecia, vitiligo, and the laboratory values defined in the inclusioncriteria

4. Major surgical procedure (as defined by the Investigator) within 28 days prior tothe first dose of Investigational Product(IP).

5. Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study intervention.

6. A WOCBP who has a positive urine pregnancy test within 72 hours prior torandomization. If the urine test is positive or cannot be confirmed as negative, aserum pregnancy test will be required.

7. Has received prior radiotherapy within 2 weeks of start of study intervention.Participants must have recovered from all radiation-related toxicities, not requirecorticosteroids, and not have had radiation pneumonitis. A 1-week washout ispermitted for palliative radiation (≤2 weeks of radiotherapy) to non-Central NervousSystem(CNS) disease.

8. Has received a live vaccine or live-attenuated vaccine within 30 days before thefirst dose of study intervention. Administration of killed vaccines is allowed.

9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of study drug.

10. Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years. Note: Participants with basal cell carcinoma of the skin,squamous cell carcinoma of the skin, urothelial cancer, or carcinoma in situ thathave undergone potentially curative therapy are not excluded.

11. Has known active Central Nervous System (CNS) metastases and/or carcinomatousmeningitis. Participants with previously treated brain metastases may participateprovided they are radiologically stable: without evidence of progression for atleast 4 weeks by repeat imaging (note that the repeat imaging should be performedduring study screening), clinically stable and without requirement of steroidtreatment for at least 14 days prior to first dose of study intervention).

12. Has active autoimmune disease that has required systemic treatment in the past 2years (i.e. with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment and is allowed.

13. Has a history of or current(non-infectious) pneumonitis/interstitial lung diseasethat required steroids

14. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIVtesting is required unless mandated by local health authority.

15. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA)and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA)infection.

• Note: Hepatitis B and C screening tests are not required unless:

• Known history of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection

• As mandated by local health authority

16. Known active infection requiring systemic therapy.

• Active infection including tuberculosis

• Active hepatitis B (HBsAg reactive and HBV DNA is detected)

• Active hepatitis C (anti-HCV reactive and HCV RNA [qualitative] is detected)

• Human immunodeficiency virus infection

17. Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of trial treatment.

18. Known allergy or hypersensitivity to any of the study drugs or any of the study drugexcipients.

19. Has had an allogenic tissue/solid organ transplant.

20. Has a history or current evidence of any condition, therapy, or laboratoryabnormality or other circumstance that might confound the results of the study,interfere with the participant's participation for the full duration of the study,such that it is not in the best interest of the participant to participate, in theopinion of the treating investigator.

21. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.