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Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04579757
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : September 27, 2021
Sponsor:
Collaborator:
BeiGene
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE September 2, 2020
First Posted Date  ICMJE October 8, 2020
Last Update Posted Date September 27, 2021
Actual Study Start Date  ICMJE March 5, 2021
Estimated Primary Completion Date February 27, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2020)
  • Incidence of dose limiting toxicity [ Time Frame: up to 60 days ]
    The primary outcome during dose escalation will be the incidence rate of dose limiting toxicities
  • Objective response rate (ORR) [ Time Frame: up to 2 years ]
    The primary outcome of dose expansion will be objective response rate (ORR) in patients with advanced solid tumors when treated with surufatinib in combination with tislelizumab in each cohort
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2020)
  • Progression Free Survival (PFS) [ Time Frame: up to 6 months ]
    the duration between the enrollment date and the first disease progression (PD) or death (whichever comes first).
  • Maximum plasma concentrations of surufatinib and tislelizumab with blood sampling [ Time Frame: up to 18 months ]
    Blood samples will be taken to measure levels of study drug
  • To evaluate the safety, in subjects, treated with surufatinib and tislelizumab [ Time Frame: up to 2 years ]
    Adverse events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
  • Disease Control Rate (DCR) [ Time Frame: Up to 24 months ]
    The incidence of complete response, partial response and stable disease
  • Duration of Response (DoR) [ Time Frame: up to 24 months ]
    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
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 24 months ]
    The incidence of partial response and stable disease
  • Time to Response (TTR) [ Time Frame: up to 24 months ]
    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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors
Official Title  ICMJE An Open-Label Phase Ib/II Study of Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Solid Tumor
  • Colorectal Cancer
  • Neuroendocrine Tumors
  • Small Cell Lung Cancer
  • Gastric Cancer
  • Soft Tissue Sarcoma
Intervention  ICMJE
  • Drug: Surufatinib and Tislelizumab _ Part 1
    Part 1 (all cohorts): oral surufatinib at a dose based on cohort level and intravenous tislelizumab at a 200-mg dose
    Other Name: HMPL-012, sulfatinib, BGB-A317
  • Drug: Surufatinib and Tislelizumab _ Part 2
    Part 2 (all cohorts): oral surufatinib at the RP2D dose selected in Part 1 and intravenous tislelizumab at a 200-mg dose
    Other Name: HMPL-012, sulfatinib, BGB-A317
Study Arms  ICMJE
  • Experimental: Surufatinib and tislelizumab (dose escalation_Part 1)
    In 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).
    Intervention: Drug: Surufatinib and Tislelizumab _ Part 1
  • Experimental: Surufatinib and tislelizumab (indication specific_Part 2)
    In 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
    Intervention: Drug: Surufatinib and Tislelizumab _ Part 2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 4, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2023
Estimated Primary Completion Date February 27, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Leslie Callahan 973-826-5578 lesliec@hmplglobal.com
Contact: Chris Tucci 973-786-2634 Christucci@hmplglobal.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04579757
Other Study ID Numbers  ICMJE 2020-012-GLOB1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE BeiGene
Investigators  ICMJE
Study Director: John Kauh, MD Hutchison
PRS Account Hutchison Medipharma Limited
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP