Clinical trial NCT03941873: 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
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 Hepatocellular Carcinoma or Gastric/Gastroesophageal Junction Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Hepatocellular
Gastric/Gastroesophageal Junction Cancer
Keywords: Carcinoma
HCC
G/GEJ Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-05-08
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to approximately 4 years and 1 month
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 4 years and 1 month
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to approximately 4 years and 1 month
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 4 years and 1 month
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 4 years and 1 month
measure: Maximum Plasma Concentration (Cmax) for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21) (21 days in each cycle)
measure: Time to Maximum Plasma Concentration (Tmax) for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
measure: Clearance After Oral Administration (CL/F) for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
measure: Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
measure: Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
measure: Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib
timeFrame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
measure: Plasma Concentrations of Sitravatinib
timeFrame: Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle)
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University Wuhan
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Nanjing
country: China
facility: General Hospital of Eastern Theatre Command Qihuaiyuan Branch(the St Hospital of Chinese Pla)
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital Branch Hospital
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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
citation: 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.