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

Carcinoma, Hepatocellular Clinical Trial

Official title:

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 HCC or GC/GEJC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03941873
• Other study ID #: BGB-900-104
• Secondary ID: CTR20182149
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 28, 2019
• Est. completion date: March 31, 2023

Study information

• Verified date: April 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is 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 or gastric/gastroesophageal junction cancer.

Description:

This is 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 will receive study treatment (s) until progressive disease (PD), unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. This study consists of the following phases.

Phase 1 (Dose escalation for sitravatinib as monotherapy and in combination with tislelizumab): Two dose levels of sitravatinib as monotherapy, 80 mg once daily and 120 mg once daily, will be evaluated in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer. A modified 3+3 design will be used in the dose escalation. Approximately 6 to 12 DLT evaluable participants will be treated with sitravatinib as monotherapy. The combination dose escalation of sitravatinib (80 mg once daily and 120 mg once daily; modified 3+3 design) with tislelizumab (200 mg every 3 weeks, in both cohorts) will be evaluated in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer. Approximately 12 to 24 DLT evaluable participants will be treated with sitravatinib in combination with tislelizumab.

Phase 2 (Dose expansion for sitravatinib as monotherapy and in combination with tislelizumab): Approximately 20 participants will be enrolled in each cohort. There will be a total of 4 cohorts in the study.

• Cohort A: Anti-PD-1/PD-L1 Antibody Naïve or Refractory/Resistant HCC

• Cohort B: Anti-PD-1/PD-L1 antibody naive HCC

• Cohort C: Anti-PD-1/PD-L1 antibody refractory/resistant HCC

• Cohort D: Anti-PD-1/PD-L1 antibody naive G/GEJ cancer

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/GC/GEJC

• 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 ICF (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

• History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc

• Severe chronic or active infections (including tuberculosis infection, etc) 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 AEs 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Gastric/Gastroesophageal Junction Cancer

Intervention

Drug:
• Sitravatinib
Study participants will receive sitravatinib capsule once daily
• Sitravatinib plus Tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
• Sitravatinib
Study participants will receive sitravatinib capsule once daily.
• Sitravatinib and tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
• Sitravatinib and tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
• Sitravatinib and tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Fujian Medical university union hospital	Fuzhou	Fujian
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	The First affiliated hospital of Nanchang University	Nanchang	Jiangxi
China	The 81st Hospital of Chinese PLA	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Hubei cancer hospital	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0		Up to approximately 3 years
Primary	Phase 2: Objective response rate (ORR)	ORR based on RECIST v1.1 by investigator	Up to approximately 3 years