Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

Prior treatment

• Adverse events (AEs) due to previous anti-tumor therapy has not recovered to Common Terminology Criteria for Adverse Event (CTCAE) ≤Grade 1;
• Previous treatment with surufatinib;
• Brain metastases and/or leptomeningeal disease and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of SD for 14 days or longer; subjects requiring steroids within 4 weeks prior to start of study treatment will be excluded;
• Arterial thrombosis or thromboembolic events (including stroke and/or transient ischemic attack) within 12 months prior to first dosing;

Other illness

• Uncontrollable hypertension;
• History or presence of a serious hemorrhage (>30 ml within 3 months), hemoptysis (>5 ml blood within 4 weeks) or life threatening thromboembolic event within 6 months;
• Clinically significant cardiovascular disease;
• Any clinically significant active infection, including, but not limited to, known human immunodeficiency virus (HIV) infection;
• Active autoimmune diseases or history of autoimmune diseases that may relapse with the following exceptions:
  • Controlled Type 1 diabetes
  • Hypothyroidism (provided it is managed with hormone-replacement therapy only)
  • Controlled celiac disease
  • Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
  • Any other disease that is not expected to recur in the absence of external triggering factors.
• History of deep venous thrombosis within 6 months;
• Any condition by which investigators judge patients not suitable to participate in this study.

Lab values

• Part 2 subjects with CRC , NETs and STS any previous treatment with anti-PD-1, anti PD-L1/L2 antibodies, anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) antibody, or any other antibody acting on T cell costimulatory or checkpoint pathway;

Other

• Female patients who are pregnant or breastfeeding;

• Willing and able to provide informed consent
• ≥18 years of age
• Part 1-have evaluable lesions (according to Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1])
• Part 2-have measurable lesions (according to RECIST v1.1)
• Have a performance status of 0 or 1 on the ECOG scale
• For female subjects of childbearing potential and male patients with partners of childbearing potential, agreement to use a highly effective form(s) of contraception
  • Dose Escalation:
• Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type,.
  • Dose Expansion:
• Histologically or cytologically documented, locally advanced or metastatic:
  • Cohort A: adenocarcinoma of the colon or rectum that is microsatellite stable. Subjects must have progressed on, or had intolerable toxicity to, at least 3 prior regimens of standard chemotherapy.
  • Cohort B: progressive, low or intermediate grade (grade 1 or grade 2) NETs of thoracic or GEP origins. Subjects must have radiological documentation of progression of disease in the last 6 months and must have progressed on at least one line of standard therapy for metastatic disease.
  • Cohort C: SCLC that has progressed on standard first line chemotherapy treatment.
  • Cohort D: adenocarcinoma of the stomach or gastroesophageal junction and have progressed on at least 2 prior lines of therapy. Tumor stain for PD-L1 by Combined Positive Score (CPS) ≥5%.
  • Cohort E: ASPS or UPS. Subjects must have radiological documentation of disease progression in the last 3 months and have progressed on at least one line of standard therapy or refused standard frontline cytotoxic chemotherapy.
  • Cohort F: Anaplastic thyroid cancer that is considered not curable by resection. Patients with a BRAFV600E mutation must have previously been treated with 1 line of systemic therapy with a BRAF-targeted therapy.