Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

NCT ID: NCT04579757

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-05
• Study Completion Date: 2024-08-27

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.

Conditions

Metastatic Solid Tumor; Colorectal Cancer; Neuroendocrine Tumors; Small Cell Lung Cancer; Gastric Cancer; Soft Tissue Sarcoma; Anaplastic Thyroid Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Surufatinib and Tislelizumab _ Part 1

Intervention Type: DRUG

Part 1 (all cohorts): oral surufatinib at a dose based on cohort level and intravenous tislelizumab at a 200-mg dose

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

Group Type: EXPERIMENTAL

Surufatinib and Tislelizumab _ Part 2

Intervention Type: DRUG

Part 2 (all cohorts): oral surufatinib at the RP2D dose selected in Part 1 and intravenous tislelizumab at a 200-mg dose

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

HMPL-012, sulfatinib, BGB-A317; HMPL-012, sulfatinib, BGB-A317

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: collaborator

Hutchmed

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Schelman, MD

Role: STUDY_CHAIR

Hutchmed

Locations

Arizona Oncology Associated, PC-HOPE

Tucson, Arizona, United States

City of Hope

Duarte, California, United States

Rocky Mountain Cancer Centers Midtown

Denver, Colorado, United States

Johns Hopkins University - Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States

Holden Comprehensive Cancer Center, University of Iowa

Iowa City, Iowa, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

University of Pennsylvania, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Prisma Health - Upstate (ITOR)

Greenville, South Carolina, United States

Sarah Cannon

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology, P.A.

Fort Worth, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Texas Oncology, P.A.

Tyler, Texas, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-012-GLOB1

Identifier Type: -

Identifier Source: org_study_id