Phase 2
Completed N=111
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
Carcinoma, Hepatocellular · Gastric Cancer
Source: ClinicalTrials.gov NCT03941873 ↗
Enrolled (actual)
111
Serious AEs
36.9%
Results posted
Oct 2024
Primary outcomePrimary: Number of Participants With Adverse Events — 3; 24; 3; 78 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events |
3; 24; 3; 78; 1; 7 | — |
| PRIMARY Objective Response Rate (ORR) |
25.0; 11.5; 9.5; 16.1 | — |
| SECONDARY Duration of Response (DOR) |
7.7; 5.7; NA; 5.5 | — |
| SECONDARY Disease Control Rate (DCR) |
90.0; 84.6; 81.0; 71.0 | — |
| SECONDARY Progression-free Survival (PFS) |
6.8; 6.8; 4.2; 3.6 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) for Sitravatinib |
27.11; 45.47; 37.02; 51.07; 63.98; 69.30 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) for Sitravatinib |
10.0; 7.04; 10.0; 7.58; 6.00; 3.04 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib |
397.95; 761.95; 604.63; 840.74; 1276.52; 1364.56 | — |
| SECONDARY Clearance After Oral Administration (CL/F) for Sitravatinib |
92.58; 35.23; 82.77; 63.76; 29.14; 78.31 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib |
535.82; 686.11; 639.49; 1254.71; 2745.23; 1532.33 | — |
| SECONDARY Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib |
NA; 3.94 | — |
| SECONDARY Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib |
2.36; 2.12; 1.51; 1.48 | — |
| SECONDARY Plasma Concentrations of Sitravatinib |
31.64; 48.12; 23.54; 77.40; 35.95; 54.05 | — |
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.
Data sourced from ClinicalTrials.gov (NCT03941873). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.