Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

Phase 2TerminatedNCT04579757

Hutchmed87 enrolled

Overview

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

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

Surufatinib and Tislelizumab _ Part 1DRUG

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 2DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (18)

Arizona Oncology Associated, PC-HOPE

Tucson, Arizona, United States

City of Hope

Duarte, California, United States

Outcomes

Primary Outcomes

Dose Escalation Phase: Number of Patients With Dose-Limiting Toxicities (DLTs)

According to National Cancer Institute Common Terminology Criteria for Adverse Events(AEs) version (v)5.0,DLT was defined as any of the following AEs during DLT observation period: Nonhematologic toxicities:grade 3 or higher nonhematologic toxicity, except for grade 3 fatigue lasting \<7 days, grade 3 rash returning to baseline or ≤grade 1 within 7 days with treatment, grade 3 hypertension downgraded to ≤grade 1 within 7 days with therapy, grade 3 endocrinopathy controlled by hormonal replacement with no hospitalization and resolving to ≤grade 1 within 7 days, grade 3 or higher amylase or lipase elevation without symptoms of pancreatitis, grade 3 nausea/vomiting or diarrhea for \<72 hours with care, grade 3 or higher electrolyte abnormality lasting up to 72 hours and resolving with treatment. Hematologic toxicities: grade 3 or higher febrile neutropenia, grade 4 neutropenia and grade 4 thrombocytopenia lasting \>7 days, grade 3 thrombocytopenia with severe bleeding, and grade 4 anemia.

Time frame: From the first dose of study drug (Day 1) up to Day 21 of Cycle 1 (cycle duration: 3 weeks)

Dose Escalation Phase: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation

An AE was any untoward medical occurrence in a clinical study patient temporally associated with the use of a study treatment in humans, whether or not considered related to the treatment. An AE was considered "serious" if, in the view of either the investigator or sponsor, it resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, was a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that started or worsened in severity on or after the first dose of study treatment and up to 30 days after the date of last study treatment administration.

Time frame: From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 9 months

Dose Expansion Phase: Objective Response Rate (ORR)

ORR was defined as the percentage of patients with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. BOR was defined as the best response recorded from the start of study treatment until documented RECIST v1.1 progression or the start date of new anticancer therapy, whichever came first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Data from ClinicalTrials.gov

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Secondary Outcomes

Dose Escalation Phase: Objective Response Rate

ORR was defined as the percentage of patients with a confirmed BOR of CR or PR as determined by the investigator using RECIST v1.1. BOR was defined as the best response recorded from the start of study treatment until documented RECIST v1.1 progression or the start date of new anticancer therapy, whichever came first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.