Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

Sponsor

Hutchison Medipharma Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04579757

Collaborator

BeiGene (Industry)

135

Enrollment

Locations

Arms

39.9

Anticipated Duration (Months)

7.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Solid Tumor Colorectal Cancer Neuroendocrine Tumors Small Cell Lung Cancer Gastric Cancer Soft Tissue Sarcoma Anaplastic Thyroid Cancer	Drug: Surufatinib and Tislelizumab _ Part 1 Drug: Surufatinib and Tislelizumab _ Part 2	Phase 1/Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

135 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 5, 2021

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
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).	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 Names: HMPL-012, sulfatinib, BGB-A317
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	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 Names: HMPL-012, sulfatinib, BGB-A317

Arm

Intervention/Treatment

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).

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 Names:

HMPL-012, sulfatinib, BGB-A317

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

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 Names:

HMPL-012, sulfatinib, BGB-A317

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicity [up to 60 days]
The primary outcome during dose escalation will be the incidence rate of dose limiting toxicities
Objective response rate (ORR) [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

Secondary Outcome Measures

Progression Free Survival (PFS) [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 [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 [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) [Up to 24 months]
The incidence of complete response, partial response and stable disease
Duration of Response (DoR) [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) [Up to 24 months]
The incidence of partial response and stable disease
Time to Response (TTR) [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).
Overall Survival [up to 36 months]
The period from date of enrollment to date of death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

Adverse events (AEs) due to previous anti-tumor therapy has not recovered to Common Terminology Criteria for Adverse Event (CTCAE) ≤Grade 1;
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;
Previous treatment with surufatinib;
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;
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;
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.
Arterial thrombosis or thromboembolic events (including stroke and/or transient ischemic attack) within 12 months prior to first dosing;
History of deep venous thrombosis within 6 months;
Female patients who are pregnant or breastfeeding;
Any condition by which investigators judge patients not suitable to participate in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associated, PC-HOPE	Tucson	Arizona	United States	85711
2	City of Hope	Duarte	California	United States	91010
3	Rocky Mountain Cancer Centers Midtown	Denver	Colorado	United States	80218
4	Johns Hopkins University - Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
5	Emory University - Winship Cancer Institute	Atlanta	Georgia	United States	30322
6	Holden Comprehensive Cancer Center, University of Iowa	Iowa City	Iowa	United States	52242
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
8	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
9	University of Pennsylvania, Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19104
10	Prisma Health - Upstate (ITOR)	Greenville	South Carolina	United States	29605
11	Sarah Cannon	Nashville	Tennessee	United States	37203
12	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
13	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
14	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
15	Texas Oncology, P.A.	Fort Worth	Texas	United States	76104
16	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77079
17	Texas Oncology, P.A.	Tyler	Texas	United States	75702
18	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031