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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)

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ClinicalTrials.gov Identifier: NCT03941873
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief 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.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Gastric/Gastroesophageal Junction Cancer Drug: Sitravatinib Drug: Sitravatinib plus Tislelizumab Drug: Sitravatinib and tislelizumab Phase 1 Phase 2

Detailed 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 28, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : October 2022

Arm Intervention/treatment
Experimental: Sitravatinib monotherapy
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 to confirm recommended Phase 2 dose (RP2D)
Drug: Sitravatinib
Study participants will receive sitravatinib capsule once daily

Experimental: Sitravatinib plus Tislelizumab
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 unresectable locally advanced or metastatic HCC or G/GEJ cancer participants . If the combination dose of 80 mg sitravatinib and 200 mg tislelizumab has been declared tolerable, the dose of sitravatinib will be escalated to 120 mg and tislelizumab will remain fixed at 200 mg. Approximately 12 to 24 evaluable participants will be treated. The dose of tislelizumab during dose escalation for the combination will be kept fixed at 200 mg
Drug: Sitravatinib plus Tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Experimental: Anti-PD-1/PD-L1 Antibody Naïve or R/R HCC (Monotherapy) Drug: Sitravatinib
Study participants will receive sitravatinib capsule once daily.

Experimental: Anti-PD-1/PD-L1 antibody naive HCC(Combination) Drug: Sitravatinib and tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Experimental: Anti-PD-1/PD-L1 antibody refractory/resistant HCC Drug: Sitravatinib and tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Experimental: Anti-PD-1/PD-L1 antibody naive G/GEJ cancer Drug: Sitravatinib and tislelizumab
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.




Primary Outcome Measures :
  1. Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0 [ Time Frame: Up to approximately 3 years ]
  2. Phase 2: Objective response rate (ORR) [ Time Frame: Up to approximately 3 years ]
    ORR based on RECIST v1.1 by investigator



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03941873


Contacts
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Contact: BeiGene +1-877-828-5568 clinicaltrials@beigene.com

Locations
Show Show 22 study locations
Sponsors and Collaborators
BeiGene
Investigators
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Principal Investigator: Jin Li, PhD Shanghai East Hospital
Principal Investigator: Shukui Qin, MD The 81st hospital of Chinese PLA
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03941873    
Other Study ID Numbers: BGB-900-104
CTR20182149 ( Other Identifier: Center for drug Drug Evaluation, NMPA )
First Posted: May 8, 2019    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by BeiGene:
Carcinoma
HCC
G/GEJ Cancer
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases