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

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ClinicalTrials.gov Identifier: NCT03666143
Recruitment Status : Not yet recruiting
First Posted : September 11, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:

This is an open-label, multicenter, non-randomized Phase 1b clinical trial for patients with histologically or cytologically confirmed locally advanced or metastatic tumors including non- squamous NSCLC, RCC, or OC.

All patients will receive sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until occurrence of PD, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor.

There will be 5 cohorts in the study. Approximately 20 patients will be enrolled into each cohort. The patients will be enrolled according to their tumor type and prior anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody treatment.

  • 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 (China-only): Metastatic or advanced RCC without prior systemic therapy
  • Cohort E: Anti-PD-1/PD-L1 antibody naïve recurrent and platinum resistant Epithelial OC A Safety Monitoring Committee (SMC) will review the safety, tolerability, and pharmacology data from the initial 6 patients (regardless of assigned cohort) that complete the first treatment cycle in Australia. Recruitment will be on hold in Australia until these data have been reviewed. For participating China sites only, the initial 6 patients enrolled in China regardless of assigned cohort will have their safety, tolerability, and pharmacology data reviewed by the SMC. Recruitment in China only will be on hold until the data have been reviewed. The SMC may assess the combination regimen as safe, but may also decide to evaluate a dosing regimen that was not predefined or not previously studied, if evaluation of toxicity at such a dose is desired.

Condition or disease Intervention/treatment Phase
Non-squamous, Non-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma (RCC), and Ovarian Cancer (OC) Drug: Sitravatinib Tislelizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2021


Arm Intervention/treatment
Experimental: Anti-PD-1/PD-L1 antibody refractory/resistant NSCLC Drug: Sitravatinib Tislelizumab
sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks

Experimental: Anti-PD-1/PD-L1 antibody naïve NSCLC Drug: Sitravatinib Tislelizumab
sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks

Experimental: Anti-PD-1/PD-L1 antibody refractory/resistant RCC Drug: Sitravatinib Tislelizumab
sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks

Experimental: Metastatic or advanced RCC without prior systemic therapy Drug: Sitravatinib Tislelizumab
sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks

Experimental: Anti-PD-1/PD-L1 naïve recurrent / platinum resistant OC Drug: Sitravatinib Tislelizumab
sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks




Primary Outcome Measures :
  1. Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0 [ Time Frame: All AEs and SAEs will be reported until either 30 days after last dose of study drug(s) or initiation of new anticancer therapy, whichever occurs first. Immune-related should be reported until 90 days after the last dose of tislelizumab ]


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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

Inclusion Criteria:

Each patient eligible to participate in this study must meet all of the following criteria:

  1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
  2. 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)
  3. At least 1 measurable lesion as defined by RECIST v1.1 Note: Selected target lesion(s) must meet one of these criteria: 1) not previously treated with local therapy or 2) within the field of prior local therapy but with subsequent progression as per RECIST v1.1.
  4. Agreement to provide archival tumor tissue (formalin-fixed paraffin-embedded block [FFPE] with tumor tissue or approximately 15 unstained slides), if available, and blood samples for molecular analysis. Note: If archival tumor tissue is not available or of sufficient quantity, an optional fresh biopsy is highly recommended. • Tumor tissue needs to originate from core or punch biopsy. • Tumor tissue from fine-needle aspiration is not acceptable.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 (Appendix 4)
  6. Adequate hematologic and end-organ function, as defined by the following laboratory values (obtained ≤ 7 days before first dose): a. Patients must not have required a blood or platelet transfusion or growth factor support ≤ 14 days before sample collection i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelets ≥ 75 x 109/L iii. Hemoglobin ≥ 90 g/L b. Serum creatinine ≤ 1.5 x upper limit of normal (ULN), or estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 8) c. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN, or AST and ALT ≤ 5.0 x ULN for patients with documented liver metastases d. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome) e. International normalized ratio (INR) ≤ 1.5 or prothrombin time ≤ 1.5 x ULN f. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
  7. 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
  8. 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 Cohort-Specific Inclusion Criteria Cohort A, Cohort B: Metastatic, non-squamous NSCLC
  9. Histologically or cytologically confirmed, Stage IV non-squamous NSCLC 10. Mixed histology (ie, squamous and non-squamous) is allowed if the major histological component is non-squamous. • Patients with disease known to be positive for epidermal growth factor receptor (EGFR), c-ros oncogene 1 receptor tyrosine kinase 1 (ROS1), anaplastic lymphoma kinase (ALK) mutations or ALK fusions are excluded. • For undocumented cases, fresh or archival tumor tissue is required for central confirmation of wild type EGFR status.

11. ≤ 2 lines of systemic therapy Cohort A: Anti-PD-1/PD-L1 antibody refractory or resistant metastatic, non-squamous NSCLC 12. Radiographic progression per RECIST v1.1 on or after anti-PD-1/PD-L1 therapy as the most recent treatment for metastatic NSCLC 13. No other prior immunotherapies, including, but not limited to, anti-CTLA-4, anti-OX40 and anti-CD137 Cohort B: Anti-PD-1/PD-L1 antibody naïve metastatic, non-squamous NSCLC 14. Radiographic progression per RECIST v1.1 on or after systemic treatment for metastatic NSCLC without prior exposure to anti-PD-1/PD-L1 agent Cohort C, Cohort D: Metastatic or advanced Renal Cell Carcinoma (RCC) 15. Histologically or cytologically confirmed metastatic or advanced clear cell RCC, or RCC with a primary clear cell component Cohort C: Anti-PD-1/PD-L1 antibody refractory or resistant metastatic or advanced RCC 16. Radiographic progression per RECIST v1.1 on or after anti-PD-1/PD-L1 therapy as the most recent treatment for mRCC 17. ≤ 2 lines of systemic therapy including anti-PD-1/PD-L1 antibody treatment 18. No other prior immunotherapies, including, but not limited to, anti-CTLA-4, anti-OX40 and anti-CD137 Cohort D: Metastatic or advanced RCC without prior systemic therapy Note: Cohort D will only enroll in China. 19. Systemic therapy is not available, is considered not suitable, or has been refused by the patient 20. Prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed > 12 months prior to enrollment.

Cohort E: Anti-PD-1/PD-L1 antibody naïve recurrent and platinum-resistant Epithelial Ovarian Cancer (OC) Note: Resistant to platinum-based therapy is defined as relapse 1-6 months after last dose of platinum-based treatment.

21. Histologically confirmed advanced ovarian cancer 22. No platinum-refractory disease (PD < 1 month of last dose of platinum-based chemotherapy) 23. No prior exposure to anti-PD-1/PD-L1 agent

Exclusion Criteria:

  • Patients who meet any of the following criteria are not eligible to enroll:

    1. Unacceptable toxicity on prior anti-PD-1/PD-L1 treatment, defined as follows: a. ≥ Grade 3 AE related to anti-PD-1/PD-L1 b. ≥ Grade 2 immune-related AE associated with anti-PD-1/PD-L1 unless the AE resolved or was well controlled by withholding the anti-PD-1/PD-L1 and/or treatment with steroids, with the exception of prior colitis, encephalitis, myocarditis, hepatitis, uveitis and pneumonitis, which are exclusionary. c. CNS or ocular AE of any grade related to anti-PD-1/PD-L1 Note: Patients with a prior endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
    2. Active leptomeningeal disease or uncontrolled brain metastasis. Patients with equivocal findings or with confirmed brain metastases are eligible for enrollment provided that they are asymptomatic and radiologically stable without the need for corticosteroid treatment for ≥ 4 weeks before first dose of study drugs. • Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. o Following treatment, these patients may then be eligible, provided all other criteria, including those for patients with a history of brain metastases, are met.
    3. Active autoimmune diseases or history of autoimmune diseases that may relapse (Appendix 5) Note: Patients with the following diseases are not excluded and may proceed to further screening: a. Controlled Type I diabetes b. Hypothyroidism (provided it is managed with hormone replacement therapy only) c. Controlled celiac disease d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia) e. Any other disease that is not expected to recur in the absence of external triggering factors
    4. Any active malignancy ≤ 2 years before first dose of study drugs except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
    5. 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 Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded: a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) b. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)
    6. Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before first dose of study drugs
    7. History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases, including pulmonary fibrosis, acute lung diseases, etc.
    8. 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
    9. Known history of HIV infection
    10. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA > 500 IU/mL or active hepatitis C (HCV) carriers Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL), and cured hepatitis C patients can be enrolled.
    11. Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs
    12. Prior allogeneic stem cell transplantation or organ transplantation
    13. Any of the following cardiovascular risk criteria: a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before first dose of study drugs b. Symptomatic pulmonary embolism ≤ 28 days before first dose of study drugs c. Any history of acute myocardial infarction ≤ 6 months before first dose of study drugs d. Any history of heart failure meeting New York Heart Association Classification (NYHA) III or IV (Appendix 7) ≤ 6 months before first dose of study drugs e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before first dose of study drugs f. Any history of cerebrovascular accident ≤ 6 months before first dose of study drugs g. QTc interval (corrected by Fridericia's method) > 450 msec Note: If QTc interval is > 450 msec on initial ECG, a follow up ECG will be performed to confirm result h. Cardiac left ventricular ejection fraction (LVEF) ≤ lower limit of normal (LLN) as assessed by echocardiography (ECHO). The same modality used at baseline must be applied for subsequent evaluations. i. Any episode of syncope or seizure ≤ 28 days before first dose of study drugs
    14. Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
    15. Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container
    16. Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring within 6 months before first dose of study drugs
    17. Any systemic chemotherapy within 28 days of the first dose of study drugs or immunotherapy (eg, interleukin, interferon, thymoxin, etc.), hormone therapy, targeted therapy, or any investigational therapies within 14 days or 5 half-lives (whichever is shorter) of first dose of study drugs
    18. Any herbal medicine used to control cancer within 14 days of first dose of study drugs
    19. Toxicities (as a result of prior anticancer therapy) that have not improved to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
    20. Administration of live vaccine ≤ 4 weeks prior to first dose of study drugs Note: seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
    21. Underlying medical conditions or alcohol or drug abuse or dependence that will be unfavorable for the administration of study drugs or affect the explanation of drug toxicity or AEs; or expected insufficient compliance during the study according to investigator's judgement
    22. Concurrent participation in another therapeutic clinical trial
    23. Inability to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
    24. Spinal cord compression in one or more of the following criteria a. Not definitively treated with surgery and/or radiation b. Treated but without evidence that disease has been clinically stable for > 2 weeks prior to first dose of study drugs
    25. Pregnant or breastfeeding woman

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): NCT03666143


Contacts
Contact: Ning Tang 86-10-8567 9808 clinicaltrails@beigene.com

Locations
Australia, New South Wales
Blacktown Cancer and Haematology Centre Not yet recruiting
Blacktown, New South Wales, Australia
Contact: Bo Gao         
Australia, Queensland
ICON Cancer Foundation Not yet recruiting
South Brisbane, Queensland, Australia
Contact: Jeffrey Goh         
Australia, Victoria
Austin Hospital Not yet recruiting
Heidelberg, Victoria, Australia
Contact: Hui Gan         
Monash Health Not yet recruiting
Melbourne, Victoria, Australia
Contact: Benjamin Markman         
Nucleus Network Not yet recruiting
Melbourne, Victoria, Australia
Contact: Mark Voskoboynik         
Australia, Western Australia
Linear Clinical Research Limited Not yet recruiting
Perth, Western Australia, Australia
Contact: Michael Millward         
China, Beijing
Beijing Cancer Hospital Not yet recruiting
Beijing, Beijing, China
Contact: Jun Guo         
Cancer Hospital Chinese Academy of Medical Science Not yet recruiting
Beijing, Beijing, China
Contact: Aiping Zhou         
Peking University First Hospital Not yet recruiting
Beijing, Beijing, China
Contact: Zhisong He         
China, Guangdong
Guangdong General Hospital Not yet recruiting
Guangzhou, Guangdong, China
Contact: Qing Zhou         
Sun Yat-Sen University Cancer Center Not yet recruiting
Guangzhou, Guangdong, China
Contact: Fangjian Zhou         
China, Jilin
The First Hospital of Jilin University Not yet recruiting
Changchun, Jilin, China
Contact: Jiuwei Cui         
China, Shanghai
Renji Hospital Shanghai Jiaotong University School of Medicine Not yet recruiting
Shanghai, Shanghai, China
Contact: Yiran Huang         
China, Tianjin
Tianjin Medical University Cancer Institute & Hospital Not yet recruiting
Tianjin, Tianjin, China
Contact: Dingzhi Huang         
China, Zhejiang
Zhejiang Cancer Hospital Not yet recruiting
Hangzhou, Zhejiang, China
Contact: Xinmin Yu         
China
Beijing Cancer Hospital Not yet recruiting
Beijing, China
Contact: Jun Zhao         
Sponsors and Collaborators
BeiGene

Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03666143     History of Changes
Other Study ID Numbers: BGB-900-103
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs