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

NCT03941873 | Completed Phase 1 Results

• 2 other identifiers: BGB-900-104CTR20182149
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Carcinoma, Hepatocellular; Gastric/Gastroesophageal Junction Cancer

Keywords

Carcinoma; HCC; G/GEJ Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Duration of Response (DOR)

  Up to approximately 4 years and 1 month

• Disease Control Rate (DCR)

  Up to approximately 4 years and 1 month

• Progression-free Survival (PFS)

  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)

Study Arms (4)

Sitravatinib Monotherapy: 80 mg

EXPERIMENTAL

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

Sitravatinib Monotherapy: 120 mg

EXPERIMENTAL

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

Sitravatinib 80 mg + Tislelizumab

EXPERIMENTAL

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: Sitravatinib; Drug: Tislelizumab

Sitravatinib 120 mg + Tislelizumab

EXPERIMENTAL

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: Sitravatinib; Drug: Tislelizumab

Interventions

Sitravatinib DRUG

Administered orally as a capsule

Also known as: MGCD516

Sitravatinib 120 mg + Tislelizumab; Sitravatinib 80 mg + Tislelizumab; Sitravatinib Monotherapy: 120 mg; Sitravatinib Monotherapy: 80 mg

Tislelizumab DRUG

Administered intravenously

Also known as: BGB-A317, Tevimbra

Sitravatinib 120 mg + Tislelizumab; Sitravatinib 80 mg + Tislelizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (18)

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)

Guangzhou, Guangdong, 510000, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Zhongnan Hospital of Wuhan University Wuhan

Wuhan, Hubei, 430071, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

General Hospital of Eastern Theatre Command Qihuaiyuan Branch(the St Hospital of Chinese Pla)

Nanjing, Jiangsu, 210002, China

Location

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

Location

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, 110042, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital Branch Hospital

Shanghai, Shanghai Municipality, 200123, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Related Publications (2)

• 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

  RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Carcinoma

Interventions

sitravatinib; tislelizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 23, 2018
• First Posted: May 8, 2019
• Study Start: February 28, 2019
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: October 26, 2024
• Results First Posted: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (18)