Clinical trial NCT04579757: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Solid Tumor
Colorectal Cancer
Neuroendocrine Tumors
Small Cell Lung Cancer
Gastric Cancer
Soft Tissue Sarcoma
Anaplastic Thyroid Cancer
Keywords: VEGF
PD-1
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: BeiGene
First posted: 2020-10-08
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Dose Escalation Phase: Number of Patients With Dose-Limiting Toxicities (DLTs)
timeFrame: From the first dose of study drug (Day 1) up to Day 21 of Cycle 1 (cycle duration: 3 weeks)
measure: Dose Escalation Phase: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation
timeFrame: From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 9 months
measure: Dose Expansion Phase: Objective Response Rate (ORR)
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 37 months
Secondary outcomes:
measure: Dose Escalation Phase: Objective Response Rate
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 42 months
measure: Dose Escalation and Dose Expansion Phases: Progression-free Survival (PFS)
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 42 months
measure: Dose Escalation and Dose Expansion Phases: Disease Control Rate (DCR)
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 42 months
measure: Dose Escalation and Dose Expansion Phases: Clinical Benefit Rate (CBR)
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 42 months
measure: Dose Escalation and Dose Expansion Phases: Duration of Response (DoR)
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 42 months
measure: Dose Escalation and Dose Expansion Phases: Time to Response (TTR)
timeFrame: Tumor assessments performed every 6 weeks (+/-1 week) for the first 24 weeks and every 9 weeks (+/-1 week) thereafter, up to a maximum of approximately 42 months
measure: Dose Escalation and Dose Expansion Phases: Plasma Concentration of Surufatinib
timeFrame: Pre-dose on Day 1 of Cycles 1, 2, 5, 9, 17 and on Days 8 and 15 of Cycle 1; 2 to 4 hours post-dose on Days 1 and 15 of Cycle 1 (cycle duration: 3 weeks)
measure: Dose Escalation and Dose Expansion Phases: Serum Concentration of Tislelizumab
timeFrame: Preinfusion on Day 1 of Cycles 1, 2, 5, 9, 17; end of infusion on Day 1 of Cycles 1 and 5; on Days 8 and 15 of Cycle 1 (cycle duration: 3 weeks)
measure: Dose Escalation and Dose Expansion Phases: Number of Patients With Antidrug Antibodies (ADA) to Tislelizumab
timeFrame: From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 9 months for dose escalation phase and approximately 33 months for dose expansion phase
measure: Dose Expansion Phase (Cohorts A and F): Overall Survival (OS)
timeFrame: From the first dose of study treatment (Day 1) up to date of death due to any cause, up to approximately 42 months
measure: Dose Expansion Phase: Number of Patients With Treatment-Emergent Adverse Events, Treatment-Emergent Serious Adverse Events and TEAEs Leading to Treatment Discontinuation
timeFrame: From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 33 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associated, PC-HOPE
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers Midtown
state: Colorado
city: Washington
country: United States
facility: Johns Hopkins University - Sibley Memorial Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center, University of Iowa
state: Iowa
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Perelman Center for Advanced Medicine
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health - Upstate (ITOR)
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
Study officials:
affiliation: Hutchmed
name: William Schelman, MD
role: STUDY_CHAIR
References: