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

BeiGene

Status and phase: Completed; Phase 2; Phase 1

Conditions: Gastric/Gastroesophageal Junction Cancer; Carcinoma, Hepatocellular

Treatments: Drug: Sitravatinib; Drug: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03941873

BGB-900-104

CTR20182149 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 111 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 4 patient groups

Sitravatinib Monotherapy: 80 mg

Experimental group

Description:

Sitravatinib 80 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer

Treatment:

Drug: Sitravatinib

Sitravatinib Monotherapy: 120 mg

Experimental group

Description:

Sitravatinib 120 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer

Treatment:

Drug: Sitravatinib

Sitravatinib 80 mg + Tislelizumab

Experimental group

Description:

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

Treatment:

Drug: Tislelizumab

Drug: Sitravatinib

Sitravatinib 120 mg + Tislelizumab

Experimental group

Description:

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

Treatment:

Drug: Tislelizumab

Drug: Sitravatinib