A Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Participants With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma or Gastric/Gastroesophageal Junction Cancer

A Phase 1/2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib as Monotherapy and in Combination With Tislelizumab in Patients With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma or Gastric/Gastroesophageal Junction Cancer

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of sitravatinib as monotherapy and in combination with tislelizumab in participants with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC) or gastric/gastroesophageal junction (G/GEJ) cancer.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular; Gastric/Gastroesophageal Junction Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Sitravatinib

Detailed Description

This was an open-label, multicenter Phase 1/2 clinical study for participants with histologically or cytologically confirmed unresectable locally advanced or metastatic HCC or G/GEJ cancer. All participants received study treatment (s) until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University Wuhan
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • General Hospital of Eastern Theatre Command Qihuaiyuan Branch(the St Hospital of Chinese Pla)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
    • Shanghai, Shanghai, China, 200123
      • Shanghai East Hospital Branch Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/gastric cancer/GEJ cancer
• Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
• Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
• Adequate organ function
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
• Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)
• Failed current standard-of-care treatment, or standard-of-care treatment is considered not appropriate at present

Key Exclusion Criteria:

• Active leptomeningeal disease or uncontrolled brain metastasis
• Active autoimmune diseases or history of autoimmune diseases that may relapse
• Any active malignancy ≤ 2 years before first dose of study drug(s)
• History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis or acute lung diseases
• Severe chronic or active infections (including tuberculosis infection) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s)
• Known history of human immunodeficiency virus (HIV) infection
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers.
• Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
• Prior allogeneic stem cell transplantation or organ transplantation
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
• Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
• Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies
• Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for adverse events not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
• Inability to swallow capsules or disease significantly affecting gastrointestinal function
• Pregnant or breastfeeding woman

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitravatinib Monotherapy: 80 mg; Sitravatinib 80 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer	Drug: Sitravatinib; Administered orally as a capsule; Other Names: MGCD516
Experimental: Sitravatinib Monotherapy: 120 mg; Sitravatinib 120 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer	Drug: Sitravatinib; Administered orally as a capsule; Other Names: MGCD516
Experimental: Sitravatinib 80 mg + Tislelizumab; Sitravatinib 80 mg orally once daily in 21-day cycles with tislelizumab 200 mg intravenously (IV) once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer	Drug: Tislelizumab; Administered intravenously; Other Names: BGB-A317; Tevimbra; Drug: Sitravatinib; Administered orally as a capsule; Other Names: MGCD516
Experimental: Sitravatinib 120 mg + Tislelizumab; Sitravatinib 120 mg orally once daily in 21-day cycles with tislelizumab 200 mg IV once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer	Drug: Tislelizumab; Administered intravenously; Other Names: BGB-A317; Tevimbra; Drug: Sitravatinib; Administered orally as a capsule; Other Names: MGCD516

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), including relevant physical examination, electrocardiograms, and laboratory assessments. Safety analysis set is presented by dose, as prespecified in the statistical analysis plan (SAP).	Up to approximately 4 years and 1 month
Objective Response Rate (ORR)	ORR is defined as the percentage of participants whose best overall response (BOR) is the confirmed complete response (CR) or partial response (PR) assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.	Up to approximately 4 years and 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease as assessed by investigator per RECIST v1.1, or death, whichever comes first. Results are reported for indication groups with responders, defined as complete response (CR) or partial response (PR). Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.	Up to approximately 4 years and 1 month
Disease Control Rate (DCR)	DCR is defined as the percentage of participants with BOR as CR, PR, or stable disease (SD) assessed by investigator per RECIST v1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.	Up to approximately 4 years and 1 month
Progression-free Survival (PFS)	PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first. Safety analysis set is presented by indication group, as prespecified in the statistical analysis plan.	Up to approximately 4 years and 1 month
Maximum Plasma Concentration (Cmax) for Sitravatinib		Predose and up to 24 hours postdose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21) (21 days in each cycle)
Time to Maximum Plasma Concentration (Tmax) for Sitravatinib		Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib		Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Clearance After Oral Administration (CL/F) for Sitravatinib		Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib		Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib		Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib		Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Plasma Concentrations of Sitravatinib		Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Publications and helpful links

General Publications

• Zhang, F., et al. Safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab (TIS) in patients (pts) with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC). Journal of Clinical Oncology 2022 40:4_suppl, 418; Meeting Abstract, 2022 ASCO Gastrointestinal Cancers Symposium; https://doi.org/10.1200/JCO.2022.40.4_suppl.418
• Chen Z., et al. Safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab (TIS) in patients (pts) with unresectable locally advanced or metastatic gastric cancer/gastroesophageal junction cancer (GC/GEJC). Journal of Clinical Oncology 2022 40:4_suppl, 281-281; Meeting Abstract, ASCO Gastrointestinal Cancers Symposium, Abstract 281.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: December 23, 2018
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: HCC; Carcinoma; G/GEJ Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: BGB-900-104; CTR20182149 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes