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Completed

NCT Number: 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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The Second Hospital of Anhui Medical University, Hefei, Anhui, China

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sitravatinib

Drug

Administered orally as a capsule

Other names: MGCD516

Tislelizumab

Drug

Administered intravenously

Other names: BGB-A317, Tevimbra

Primary outcomes

  1. Number of Participants With Adverse Events

    Time frame: Up to approximately 4 years and 1 month

    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).

  2. Objective Response Rate (ORR)

    Time frame: Up to approximately 4 years and 1 month

    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.

Secondary outcomes

  1. Duration of Response (DOR)

    Time frame: Up to approximately 4 years and 1 month

    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.

  2. Disease Control Rate (DCR)

    Time frame: Up to approximately 4 years and 1 month

    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.

  3. Progression-free Survival (PFS)

    Time frame: Up to approximately 4 years and 1 month

    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.

  4. Maximum Plasma Concentration (Cmax) for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21) (21 days in each cycle)

  5. Time to Maximum Plasma Concentration (Tmax) for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)

  6. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)

  7. Clearance After Oral Administration (CL/F) for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)

  8. Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)

  9. Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)

  10. Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib

    Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)

  11. Plasma Concentrations of Sitravatinib

    Time frame: Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle)

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
May 8, 2019
Registry last updated
Oct 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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