AzTrials
AzTrials

Advanced Solid TumorsPhase 1NCT03666143

A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors

A Phase 1 study testing Sitravatinib and Tislelizumab in people with Advanced Solid Tumors, run by BeiGene at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This was an open-label, multicenter, non-randomized Phase 1b clinical trial for participants with histologically or cytologically confirmed locally advanced or metastatic tumors including non-squamous or squamous non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), ovarian cancer (OC), or melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Sitravatinib and Tislelizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
216 participants
Where
19 sitesin 2 countries
Study dates
1 Nov 2018to 5 Jan 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • At least 1 measurable lesion as defined by RECIST v1.1
  • Provide archival tumor tissue (formalin-fixed paraffin-embedded block [FFPE] with tumor tissue or unstained slides), if available.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
  • Adequate hematologic and end-organ function
Show all 9Show fewer
  • Participants with inactive/asymptomatic carrier, chronic, or active hepatitis B virus (HBV) must have HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at Screening
  • 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 drugs and have a negative serum pregnancy test ≤ 7 days of first dose of study drugs
  • Non-sterile 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 drugs

Who cannot join

  • Unacceptable toxicity on prior anti-PD-1/PD-L1 treatment
  • Active leptomeningeal disease or uncontrolled brain metastasis
  • Active autoimmune diseases or history of autoimmune diseases that may relapse
  • Any active malignancy ≤ 2 years
  • Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drugs
  • History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases, including pulmonary fibrosis, acute lung diseases, etc.
Show all 14Show fewer
  • 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 drugs
  • Known history of human immunodeficiency virus (HIV) infection
  • Participants with active hepatitis C infection
  • Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs
  • Prior allogeneic stem cell transplantation or organ transplantation
  • Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container
  • Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring within 6 months before first dose of study drugs
  • Concurrent participation in another therapeutic clinical trial

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

China13 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

  • Guangdong Provincial Peoples Hospital

    Guangzhou, Guangdong, 510080

  • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310016

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

  • Jinan Central Hospital

    Jinan, Shandong, 250013

  • Shandong Cancer Hospital

    Jinan, Shandong, 250117

  • Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School

    Nanjing, Jiangsu, 210008

  • The First Hospital of China Medical University

    Shenyang, Liaoning, 110001

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, Tianjin Municipality, 300060

  • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian, 361003

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

Australia6 sites

  • Blacktown Cancer and Haematology Centre

    Blacktown, New South Wales, 2148

  • Monash Health

    Clayton, Victoria, 3168

  • Austin Health

    Heidelberg, Victoria, 3084

  • Nucleus Network

    Melbourne, Victoria, 3004

  • Linear Clinical Research

    Nedlands, Western Australia, 6009

  • Icon Cancer Foundation

    South Brisbane, Queensland, 4101

Other trials in Australia

About this study

Official title: A Phase 1b Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Solid Tumors

This was an open-label, multicenter, non-randomized Phase 1b clinical trial for participants with histologically or cytologically confirmed locally advanced or metastatic tumors including non-squamous or squamous non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), ovarian cancer (OC), or melanoma.

Read the detailed description

All participants received sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks until occurrence of progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. Participants were enrolled according to their tumor type and prior anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody treatment into the following cohorts:

  • Cohort A: Anti-PD-1/PD-L1 antibody refractory/resistant metastatic, non-squamous NSCLC
  • Cohort B: Anti-PD-1/PD-L1 antibody naïve metastatic, non-squamous NSCLC
  • Cohort C: Anti-PD-1/PD-L1 antibody refractory/resistant metastatic or advanced RCC
  • Cohort D: Metastatic or advanced RCC without prior systemic therapy
  • Cohort E: Anti-PD-1/PD-L1 antibody naïve recurrent and platinum resistant epithelial OC
  • Cohort F: Anti-PD-1/PD-L1 antibody treated metastatic, squamous NSCLC
  • Cohort G: Anti-PD-1/PD-L1 antibody refractory/resistant unresectable or metastatic melanoma
  • Cohort H: PD-L1 positive, locally advanced or metastatic, non-squamous NSCLC without prior systemic treatment in the metastatic setting
  • Cohort I: PD-L1 positive, locally advanced or metastatic, squamous NSCLC without prior systemic treatment in the metastatic setting
Being tested
Sitravatinib, Tislelizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SitravatinibDrug

    Also called MGCD516

    Administered orally as a capsule

  • TislelizumabDrug

    Also called BGB-A317, Tevimbra

    Administered intravenously

Study groups in NCT03666143
Study groupRoleWhat they receive
Sitravatinib + TislelizumabExperimentalSitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
Receives: Drug: Sitravatinib; Drug: Tislelizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AEs)

    Number of participants with treatment-emergent AEs (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs; TEAE was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study drug(s) or initiation of a new anticancer therapy, whichever occurs first.

    Measured: Up to approximately 4 years and 2 months

Secondary outcomes (11)

  1. Objective Response Rate (ORR)

    ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) as determined by the investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

    Measured: Up to approximately 4 years and 2 months

  2. Duration of Response (DOR)

    DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease, whichever comes first, as assessed by the investigator using RECIST v1.1. Results are reported for cohorts with responders, defined as CR or PR. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

    Measured: Up to approximately 4 years and 2 months

  3. Disease Control Rate (DCR)

    DCR is defined as the percentage of participants with best overall response as CR, PR, or stable disease (SD) as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

    Measured: Up to approximately 4 years and 2 months

  4. Progression-free Survival (PFS)

    PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease or death, whichever comes first, as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

    Measured: Up to approximately 4 years and 2 months

  5. Maximum Plasma Concentration (Cmax) for Sitravatinib

    Measured: Predose and up to 24 hours post dose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21); 21 days per cycle

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

    Measured: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

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

    Measured: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

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

    Measured: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

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

    Measured: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

  10. Observed Accumulation Ratio (Ro) for AUC0-tau for Sitravatinib

    Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation

    Measured: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

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

    Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation

    Measured: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2018
  2. Study start1 Nov 2018
  3. Primary completion5 Jan 2023
  4. Study completion5 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
216 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03666143
Sponsor's protocol ID
BGB-900-103
Other IDs
CTR20181404
Status last verified
Oct 2024
First submitted
21 Aug 2018
Last updated
4 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Guo J, Zhou Q, Huang D, Yu X, Zhao J, Chu Q, Ma Z, Millward M, Gao B, Goh J, Markman B, Voskoboynik M, Gan H, Coward J, Chen C, Xiang X, Qui J, Xu Y, Yang L, Wu YL. A phase 1b study to assess safety, tolerability, pharmacokinetics, and preliminary antitumor activity of sitravatinib in combination with tislelizumab in patients (pts) with advanced solid tumors. Chinese Society of Clinical Oncology. 2019.

  • Zhao J, Yu X, Huang D, Ma Z, Gao B, Cui J, Chu Q, Zhou Q, Sun M, Day D, Wu J, Pan H, Wang L, Voskoboynik M, Wang Z, Liu Y, Li H, Zhang J, Peng Y, Wu YL. SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer. J Immunother Cancer. 2023 Feb;11(2):e006055. doi: 10.1136/jitc-2022-006055.

    PubMed 36808075

  • Wang X, Pan H, Cui J, Chen X, Yoon WH, Carlino MS, Li X, Li H, Zhang J, Sun J, Guo J, Cui C. SAFFRON-103: a phase Ib study of sitravatinib plus tislelizumab in anti-PD-(L)1 refractory/resistant advanced melanoma. Immunotherapy. 2024 Mar;16(4):243-256. doi: 10.2217/imt-2023-0130. Epub 2024 Jan 10.

    PubMed 38197138

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sitravatinib and Tislelizumab in people with Advanced Solid Tumors, run by BeiGene at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in China, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) (time frame: Up to approximately 4 years and 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03666143, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in