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出境医 / 临床实验 / Study of TJ011133 Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma

Study of TJ011133 Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma

Study Description
Brief Summary:
The purpose of this study is to assess the safety and tolerability of TJ011133 in participants with solid tumors and lymphoma.

Condition or disease Intervention/treatment Phase
Solid Tumor Lymphoma Drug: TJ011133 Drug: Pembrolizumab Drug: Rituximab Phase 1

Detailed Description:
This is an open-label, multi-center, multiple dose, Phase 1 study to evaluate the safety, tolerability, maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK), pharmacodynamic, and recommended Phase 2 dose (RP2D) of TJ011133, an anti-CD47 antibody, in subjects with advanced relapsed or refractory solid tumors and lymphoma. The study will be conducted in 2 parts. Part 1 comprises a single agent dose escalation (Part 1A) and 2 separate combination therapy dose escalations (Part 1B with pembrolizumab and Part 1C with rituximab) and Part 2 includes a dose expansion study.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of TJ011133 Administered Alone or in Combination With Pembrolizumab or Rituximab in Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
Actual Study Start Date : May 8, 2019
Estimated Primary Completion Date : February 21, 2022
Estimated Study Completion Date : September 23, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Part 1A - TJ011133 Monotherapy
TJ011133 alone will be administered at up to 7 dose levels (0.3, 1, 3, 10, 20, 30, 45 mg/kg) once weekly (Q1W) (the 0.3 mg/kg dose level cohort will be enrolled if a DLT in 1 out of 3 subjects is observed following the 1 mg/kg dose level)
 Drug: TJ011133
TJ011133 will be administered weekly
Experimental: Part 1B - Combination therapy of TJ011133 with pembrolizumab
TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with pembrolizumab
 Drug: TJ011133
TJ011133 will be administered weekly

Drug: Pembrolizumab
Pembrolizumab will be administered every 3 weeks
Other Name: Keytruda
Experimental: Part 1C -Combination therapy of TJ011133 with rituximab
TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab
 Drug: TJ011133
TJ011133 will be administered weekly

Drug: Rituximab
Rituximab will be administered weekly for 5 doses, then followed by monthly doses
Other Name: Rituxan, MabThera
Experimental: Part 2 - Dose Expansion
30 subjects (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 subjects with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
 Drug: TJ011133
TJ011133 will be administered weekly

Drug: Pembrolizumab
Pembrolizumab will be administered every 3 weeks
Other Name: Keytruda

Drug: Rituximab
Rituximab will be administered weekly for 5 doses, then followed by monthly doses
Other Name: Rituxan, MabThera
Outcome Measures
Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLT) [ Time Frame: 21 or 28 days, depending on Study Part ]
    Part 1A DLT period is 3 weeks, Part 1B DLT period is 3 weeks, Part 1C DLT period is 4 weeks

  2. Incidence and Severity of Adverse Events [ Time Frame: up to 100 days post last dose ]
    The CTCAE criteria will be used to assess adverse events on this trial.

  3. Maximum Tolerated Dose (MTD) for both monotherapy and combination therapy [ Time Frame: 21 or 28 days, depending on Study Part ]
    Based on DLT Definitions


Secondary Outcome Measures :
  1. Pharmacokinetic Parameters: Tmax [ Time Frame: up to 100 days post last dose ]
    Time of peak concentration (Tmax)

  2. Pharmacokinetic Parameters: Cmax [ Time Frame: up to 100 days post last dose ]
    Maximal concentration (Cmax)

  3. Pharmacokinetic Parameters: T1/2 [ Time Frame: up to 100 days post last dose ]
    Investigational Product (IP) half-life (T1/2)

  4. Pharmacokinetic Parameters: CL [ Time Frame: up to 100 days post last dose ]
    Investigational Product (IP) Clearance (CL)

  5. Pharmacokinetic (PK) Parameters: AUC∞ [ Time Frame: up to 100 days post last dose ]
    Area under the curve from time zero extrapolated to infinity (AUC∞)

  6. Anti-drug antibodies (ADA) [ Time Frame: up to 100 days post last dose ]
    Incidence and concentration of anti-drug antibodies


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

Inclusion Criteria:

  • Part 1: Subjects with advanced relapsed/refractory solid tumors and lymphoma.
  • Part 2 with Rituximab: Subjects with DLBCL or Indolent B-cell Lymphoma, with at least one measurable lesion by Lugano and available fresh metastatic biopsy sample prior to study entry.
  • Part 2 with Pembrolizumab: Subjects with locally advanced non-small-cell lung carcinoma (NSCLC) with disease progression or immune-oncology treatment naive Epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, with at least one measurable lesion defined by RECIST 1.1, and available fresh metastatic biopsy prior to study entry.
  • All Parts: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 and adequate bone marrow, renal, and liver functions.

Exclusion Criteria:

  • Subjects with known symptomatic central nervous system tumors or known central nervous system metastases or leptomeningeal disease requiring steroids. Subjects who document stable and central nervous system metastases and are off steroids for more than 4 weeks may be enrolled in the study
  • Subjects with Burkitt's lymphoma, lymphoblastic lymphoma, Richter's transformation, primary effusion lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Subjects with mantle cell lymphoma
  • Impaired cardiac function or clinically significant cardiac diseases
  • Prior treatment with CD47 or SIRPα inhibitors
  • Prior autologous stem cell transplant ≤3 months prior to starting study
  • Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning
  • Prior chimeric antigen receptor or chimeric antigen receptor T-cell therapy
  • History of autoimmune anemia or autoimmune thrombocytopenia
  • Positive Direct Antiglobulin Test
  • Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD
Contacts and Locations

Contacts
Layout table for location contacts
Contact: US Site Head 301-294-4408 us.info@i-mabbiopharma.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
I-Mab Biopharma Co. Ltd.
Investigators
Layout table for investigator information
Study Director: Claire Xu, MD, PhD I-Mab Biopharma
Tracking Information
First Submitted Date  ICMJE April 26, 2019
First Posted Date  ICMJE May 2, 2019
Last Update Posted Date May 24, 2021
Actual Study Start Date  ICMJE May 8, 2019
Estimated Primary Completion Date February 21, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • Dose Limiting Toxicities (DLT) [ Time Frame: 21 or 28 days, depending on Study Part ]
    Part 1A DLT period is 3 weeks, Part 1B DLT period is 3 weeks, Part 1C DLT period is 4 weeks
  • Incidence and Severity of Adverse Events [ Time Frame: up to 100 days post last dose ]
    The CTCAE criteria will be used to assess adverse events on this trial.
  • Maximum Tolerated Dose (MTD) for both monotherapy and combination therapy [ Time Frame: 21 or 28 days, depending on Study Part ]
    Based on DLT Definitions
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • Pharmacokinetic Parameters: Tmax [ Time Frame: up to 100 days post last dose ]
    Time of peak concentration (Tmax)
  • Pharmacokinetic Parameters: Cmax [ Time Frame: up to 100 days post last dose ]
    Maximal concentration (Cmax)
  • Pharmacokinetic Parameters: T1/2 [ Time Frame: up to 100 days post last dose ]
    Investigational Product (IP) half-life (T1/2)
  • Pharmacokinetic Parameters: CL [ Time Frame: up to 100 days post last dose ]
    Investigational Product (IP) Clearance (CL)
  • Pharmacokinetic (PK) Parameters: AUC∞ [ Time Frame: up to 100 days post last dose ]
    Area under the curve from time zero extrapolated to infinity (AUC∞)
  • Anti-drug antibodies (ADA) [ Time Frame: up to 100 days post last dose ]
    Incidence and concentration of anti-drug antibodies
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of TJ011133 Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
Official Title  ICMJE A Phase 1 Study of TJ011133 Administered Alone or in Combination With Pembrolizumab or Rituximab in Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
Brief Summary The purpose of this study is to assess the safety and tolerability of TJ011133 in participants with solid tumors and lymphoma.
Detailed Description This is an open-label, multi-center, multiple dose, Phase 1 study to evaluate the safety, tolerability, maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK), pharmacodynamic, and recommended Phase 2 dose (RP2D) of TJ011133, an anti-CD47 antibody, in subjects with advanced relapsed or refractory solid tumors and lymphoma. The study will be conducted in 2 parts. Part 1 comprises a single agent dose escalation (Part 1A) and 2 separate combination therapy dose escalations (Part 1B with pembrolizumab and Part 1C with rituximab) and Part 2 includes a dose expansion study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Lymphoma
Intervention  ICMJE
  • Drug: TJ011133
    TJ011133 will be administered weekly
  • Drug: Pembrolizumab
    Pembrolizumab will be administered every 3 weeks
    Other Name: Keytruda
  • Drug: Rituximab
    Rituximab will be administered weekly for 5 doses, then followed by monthly doses
    Other Name: Rituxan, MabThera
Study Arms  ICMJE
  • Experimental: Part 1A - TJ011133 Monotherapy
    TJ011133 alone will be administered at up to 7 dose levels (0.3, 1, 3, 10, 20, 30, 45 mg/kg) once weekly (Q1W) (the 0.3 mg/kg dose level cohort will be enrolled if a DLT in 1 out of 3 subjects is observed following the 1 mg/kg dose level)
    Intervention: Drug: TJ011133
  • Experimental: Part 1B - Combination therapy of TJ011133 with pembrolizumab
    TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with pembrolizumab
    Interventions:
    • Drug: TJ011133
    • Drug: Pembrolizumab
  • Experimental: Part 1C -Combination therapy of TJ011133 with rituximab
    TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab
    Interventions:
    • Drug: TJ011133
    • Drug: Rituximab
  • Experimental: Part 2 - Dose Expansion
    30 subjects (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 subjects with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
    Interventions:
    • Drug: TJ011133
    • Drug: Pembrolizumab
    • Drug: Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2021) 		116
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2019) 		88
Estimated Study Completion Date  ICMJE September 23, 2023
Estimated Primary Completion Date February 21, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Part 1: Subjects with advanced relapsed/refractory solid tumors and lymphoma.
  • Part 2 with Rituximab: Subjects with DLBCL or Indolent B-cell Lymphoma, with at least one measurable lesion by Lugano and available fresh metastatic biopsy sample prior to study entry.
  • Part 2 with Pembrolizumab: Subjects with locally advanced non-small-cell lung carcinoma (NSCLC) with disease progression or immune-oncology treatment naive Epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, with at least one measurable lesion defined by RECIST 1.1, and available fresh metastatic biopsy prior to study entry.
  • All Parts: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 and adequate bone marrow, renal, and liver functions.

Exclusion Criteria:

  • Subjects with known symptomatic central nervous system tumors or known central nervous system metastases or leptomeningeal disease requiring steroids. Subjects who document stable and central nervous system metastases and are off steroids for more than 4 weeks may be enrolled in the study
  • Subjects with Burkitt's lymphoma, lymphoblastic lymphoma, Richter's transformation, primary effusion lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Subjects with mantle cell lymphoma
  • Impaired cardiac function or clinically significant cardiac diseases
  • Prior treatment with CD47 or SIRPα inhibitors
  • Prior autologous stem cell transplant ≤3 months prior to starting study
  • Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning
  • Prior chimeric antigen receptor or chimeric antigen receptor T-cell therapy
  • History of autoimmune anemia or autoimmune thrombocytopenia
  • Positive Direct Antiglobulin Test
  • Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Site Head 301-294-4408 us.info@i-mabbiopharma.com
Listed Location Countries  ICMJE China,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03934814
Other Study ID Numbers  ICMJE TJ011133EDI101
KEYNOTE KN-A21 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party I-Mab Biopharma Co. Ltd.
Study Sponsor  ICMJE I-Mab Biopharma Co. Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Claire Xu, MD, PhD I-Mab Biopharma
PRS Account I-Mab Biopharma Co. Ltd.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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