Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

NCT04579757 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 2020-012-GLOB1
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 18

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).

Conditions

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

Keywords

VEGF; PD-1

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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 (11)

• Dose Escalation Phase: Objective Response Rate

  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

• Dose Escalation and Dose Expansion Phases: Progression-free Survival (PFS)

  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

• Dose Escalation and Dose Expansion Phases: Disease Control Rate (DCR)

  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

• Dose Escalation and Dose Expansion Phases: Clinical Benefit Rate (CBR)

  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

• Dose Escalation and Dose Expansion Phases: Duration of Response (DoR)

  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

Study Arms (2)

Surufatinib and tislelizumab (dose escalation_Part 1)

EXPERIMENTAL

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

Surufatinib and tislelizumab (indication specific_Part 2)

EXPERIMENTAL

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

Interventions

Surufatinib and Tislelizumab _ Part 1 DRUG

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

Also known as: HMPL-012, sulfatinib, BGB-A317

Surufatinib and tislelizumab (dose escalation_Part 1)

Surufatinib and Tislelizumab _ Part 2 DRUG

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

Also known as: HMPL-012, sulfatinib, BGB-A317

Surufatinib and tislelizumab (indication specific_Part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Hutchmed: lead
• BeiGene: collaborator

Study Sites (18)

Arizona Oncology Associated, PC-HOPE

Tucson, Arizona, 85711, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Rocky Mountain Cancer Centers Midtown

Denver, Colorado, 80218, United States

Location

Johns Hopkins University - Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Holden Comprehensive Cancer Center, University of Iowa

Iowa City, Iowa, 52242, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Prisma Health - Upstate (ITOR)

Greenville, South Carolina, 29605, United States

Location

Sarah Cannon

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology, P.A.

Fort Worth, Texas, 76104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77079, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Colorectal Neoplasms; Neuroendocrine Tumors; Small Cell Lung Carcinoma; Stomach Neoplasms; Sarcoma; Thyroid Carcinoma, Anaplastic

Interventions

surufatinib; tislelizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Stomach Diseases; Neoplasms, Connective and Soft Tissue; Carcinoma; Neoplasms, Glandular and Epithelial

Limitations and Caveats

The study was terminated based on the strategic re-evaluation of the clinical development of surufatinib in the United States and Europe with no safety concerns.

Results Point of Contact

• Title: Nicky Murray
• Organization: HUTCHMED Limited

nicolam@hutch-med.com

+44 7738 881999

Study Officials

• William Schelman, MD

  Hutchmed

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: October 8, 2020
• Study Start: March 5, 2021
• Primary Completion: April 30, 2024
• Study Completion: August 27, 2024
• Last Updated: May 8, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)