Clinical Trials /

Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

NCT04579757

Description:

This open-label, phase Ib/II study of surufatinib in combination with tislelizumab will evaluate the safety, tolerability, PK and efficacy in patients with advanced solid tumors. The study consists of 2 parts - dose finding (Part 1) and dose expansion (Part 2).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Alveolar Soft Part Sarcoma
  • Colorectal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
  • Neuroendocrine Tumor
  • Small Cell Lung Carcinoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors
  • Official Title: An Open-Label Phase Ib/II Study of Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2020-012-GLOB1
  • NCT ID: NCT04579757

Conditions

  • Metastatic Solid Tumor
  • Colorectal Cancer
  • Neuroendocrine Tumors
  • Small Cell Lung Cancer
  • Gastric Cancer
  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
Surufatinib and Tislelizumab _ Part 1HMPL-012, sulfatinib, BGB-A317Surufatinib and tislelizumab (dose escalation_Part 1)
Surufatinib and Tislelizumab _ Part 2HMPL-012, sulfatinib, BGB-A317Surufatinib and tislelizumab (indication specific_Part 2)

Purpose

This open-label, phase Ib/II study of surufatinib in combination with tislelizumab will evaluate the safety, tolerability, PK and efficacy in patients with advanced solid tumors. The study consists of 2 parts - dose finding (Part 1) and dose expansion (Part 2).

Detailed Description

      This open-label, phase Ib/II study of surufatinib in combination with tislelizumab will
      evaluate the safety, tolerability, PK and efficacy in patients with advanced solid tumors.
      The study consists of 2 parts - dose finding (Part 1) and dose expansion (Part 2).

      Part 1 will be conducted to determine the recommended phase 2 dose (RP2D) and/or the maximum
      tolerated dose (MTD) of surufatinib in combination with tislelizumab in patients with
      advanced or metastatic solid tumors who have progressed on, or are intolerant to standard
      therapies.

      Part 2 will be an open-label, multi-cohort design to evaluate the anti-tumor activity of
      surufatinib in combination with tislelizumab in patients with specific types of advanced or
      metastatic solid tumors. Patients will receive the RP2D determined in part 1 of this study.
    

Trial Arms

NameTypeDescriptionInterventions
Surufatinib and tislelizumab (dose escalation_Part 1)ExperimentalIn Part 1 (dose escalation), surufatinib and will be administered orally (PO) once daily (QD) and tislelizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W).
  • Surufatinib and Tislelizumab _ Part 1
Surufatinib and tislelizumab (indication specific_Part 2)ExperimentalIn Part 2, the indication-specific expansion portion of the study, patients will receive surufatinib at the Recommended Phase 2 Dose (RP2D) dose selected in Part 1 with 200 mg tislelizumab IV, Q3W
  • Surufatinib and Tislelizumab _ Part 2

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to provide informed consent

          2. ≥18 years of age

          3. Part 1-have evaluable lesions (according to Response Evaluation Criteria in Solid
             Tumors version 1.1 [RECIST v1.1])

          4. Part 2-have measurable lesions (according to RECIST v1.1)

          5. Have a performance status of 0 or 1 on the ECOG scale

          6. 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:

          7. Histologically or cytologically documented, locally advanced or metastatic solid
             malignancy of any type,.

             Dose Expansion:

          8. 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.

        Exclusion Criteria:

          1. Adverse events (AEs) due to previous anti-tumor therapy has not recovered to Common
             Terminology Criteria for Adverse Event (CTCAE) ≤Grade 1;

          2. 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;

          3. Previous treatment with surufatinib;

          4. Uncontrollable hypertension;

          5. 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;

          6. Clinically significant cardiovascular disease;

          7. Any clinically significant active infection, including, but not limited to, known
             human immunodeficiency virus (HIV) infection;

          8. 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;

          9. Active autoimmune diseases or history of autoimmune diseases that may relapse with the
             following exceptions:

               1. Controlled Type 1 diabetes

               2. Hypothyroidism (provided it is managed with hormone-replacement therapy only)

               3. Controlled celiac disease

               4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or
                  alopecia)

               5. Any other disease that is not expected to recur in the absence of external
                  triggering factors.

         10. Arterial thrombosis or thromboembolic events (including stroke and/or transient
             ischemic attack) within 12 months prior to first dosing;

         11. History of deep venous thrombosis within 6 months;

         12. Female patients who are pregnant or breastfeeding;

         13. Any condition by which investigators judge patients not suitable to participate in
             this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicity
Time Frame:up to 60 days
Safety Issue:
Description:The primary outcome during dose escalation will be the incidence rate of dose limiting toxicities

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:up to 6 months
Safety Issue:
Description:the duration between the enrollment date and the first disease progression (PD) or death (whichever comes first).
Measure:Maximum plasma concentrations of surufatinib and tislelizumab with blood sampling
Time Frame:up to 18 months
Safety Issue:
Description:Blood samples will be taken to measure levels of study drug
Measure:To evaluate the safety, in subjects, treated with surufatinib and tislelizumab
Time Frame:up to 2 years
Safety Issue:
Description:Adverse events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measure:Disease Control Rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:The incidence of complete response, partial response and stable disease
Measure:Duration of Response (DoR)
Time Frame:up to 24 months
Safety Issue:
Description:The duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 24 months
Safety Issue:
Description:The incidence of partial response and stable disease
Measure:Time to Response (TTR)
Time Frame:up to 24 months
Safety Issue:
Description:The period from the date of enrollment to the date when the criteria for complete response or partial response was first measured (first record shall prevail).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hutchison Medipharma Limited

Trial Keywords

  • VEGF
  • PD-1

Last Updated

October 8, 2020