Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

Colorectal Cancer Clinical Trial

Official title:

An Open-Label Phase Ib/II Study of Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04579757
• Other study ID #: 2020-012-GLOB1
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 5, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2024
• Source: Hutchmed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: June 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anaplastic Thyroid Cancer
• Colorectal Cancer
• Gastric Cancer
• Metastatic Solid Tumor
• Neoplasms
• Neuroendocrine Tumors
• Sarcoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Soft Tissue Sarcoma
• Thyroid Carcinoma, Anaplastic

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers Midtown	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Texas Oncology, P.A.	Fort Worth	Texas
United States	Prisma Health - Upstate (ITOR)	Greenville	South Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Holden Comprehensive Cancer Center, University of Iowa	Iowa City	Iowa
United States	Sarah Cannon	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania, Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Arizona Oncology Associated, PC-HOPE	Tucson	Arizona
United States	Texas Oncology, P.A.	Tyler	Texas
United States	Johns Hopkins University - Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Hutchmed	BeiGene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicity	The primary outcome during dose escalation will be the incidence rate of dose limiting toxicities	up to 60 days
Primary	Objective response rate (ORR)	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	up to 2 years
Secondary	Progression Free Survival (PFS)	the duration between the enrollment date and the first disease progression (PD) or death (whichever comes first).	up to 6 months
Secondary	Maximum plasma concentrations of surufatinib and tislelizumab with blood sampling	Blood samples will be taken to measure levels of study drug	up to 18 months
Secondary	To evaluate the safety, in subjects, treated with surufatinib and tislelizumab	Adverse events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	up to 2 years
Secondary	Disease Control Rate (DCR)	The incidence of complete response, partial response and stable disease	Up to 24 months
Secondary	Duration of Response (DoR)	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	up to 24 months
Secondary	Clinical Benefit Rate (CBR)	The incidence of partial response and stable disease	Up to 24 months
Secondary	Time to Response (TTR)	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).	up to 24 months
Secondary	Overall Survival	The period from date of enrollment to date of death	up to 36 months