Back to resultsStudy of TJ011133 in Participants With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
Primary Purpose
Solid Tumor, Lymphoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TJ011133
Pembrolizumab
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumor focused on measuring Solid Tumor, Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Part 1: Participants with advanced relapsed/refractory solid tumors and lymphoma.
- Part 2 with Rituximab: Participants with diffuse large B-cell lymphoma (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: Participants 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 Response Elevation Criteria in Solid Tumors (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:
- Participants with known symptomatic central nervous system tumors or known central nervous system metastases or leptomeningeal disease requiring steroids. Participants who document stable and central nervous system metastases and are off steroids for more than 4 weeks may be enrolled in the study.
- Participants with Burkitt's lymphoma, lymphoblastic lymphoma, Richter's transformation, primary effusion lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma.
- Participants 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.
Sites / Locations
- University of Alabama - Birmingham ID# 233979
- Mayo Clinic /ID# 233546
- Yale School of Medicine /ID# 233748
- Mayo Clinic /ID# 233977
- Horizon Oncology /ID# 234256
- University of Michigan /ID# 233976
- Henry Ford Cancer Institute/Henry Ford Hospital /ID# 234122
- Mayo Clinic /ID# 233305
- Rutgers Cancer Institute of New Jersey /ID# 232267
- NYU Langone Health /ID# 233978
- Vanderbilt-Ingram Cancer Center /ID# 233975
- Seattle Cancer Care Alliance /ID# 233749
- Beijing Cancer Hospital /ID# 241221
- Sun Yat-sen University Cancer Center /ID# 241696
- The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital) / ID# 242333
- Henan Cancer Hospital /ID# 241670
- HuBei Cancer Hospital /ID# 241673
- The Second Hospital of Dalian Medical University /ID# 241671
- Fudan University Shanghai Cancer Center /ID# 242303
- Tianjin Medical University Cancer Institute & Hospital / ID# 241728
- Zhejiang Cancer Hospital /ID# 241672
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part 1A - TJ011133 Monotherapy
Part 1B - Combination therapy of TJ011133 with pembrolizumab
Part 1C - Combination therapy of TJ011133 with rituximab
Part 2 - Dose Expansion
Arm Description
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).
TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab.
TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab.
30 participants (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 participants with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
Outcomes
Primary Outcome Measures
Dose Limiting Toxicities (DLT)
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
The CTCAE criteria will be used to assess adverse events on this trial.
Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy
Based on DLT definitions.
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status.
Secondary Outcome Measures
Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞)
Area under the curve from time zero to infinity (AUC∞).
PK: Area Under the Curve From Time Zero To The Time Of The Last Quantifiable Concentration (AUC0-t)
Area under the curve from time zero to the time of the last quantifiable concentration (AUC0-t).
PK: Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax).
PK: Time of the Maximum Observed Concentration (Tmax)
Time of the maximum observed concentration (Tmax).
PK: Terminal Elimination Half-Life (T1/2)
Investigational Product (IP) terminal elimination half-life (T1/2).
PK: Clearance (CL)
Investigational Product (IP) Clearance (CL).
PK: Volume Of Distribution (Vz)
Investigational Product (IP) volume of distribution (Vz).
PK: AUC Over A Dosing Interval (AUCtau)
AUC over a dosing interval (AUCtau).
PK: Trough Concentration (Ctrough)
Investigational Product (IP) trough concentration (Ctrough).
PK: Volume of Distribution at Steady State (Vss)
Investigational Product (IP) volume of distribution at steady state (Vss).
Immunogenicity: Anti-drug antibodies (ADA)
Incidence and concentration of anti-drug antibodies.
Efficacy: Best Overall Response (BOR)
BOR is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Efficacy: Objective Response Rate (ORR)
ORR is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Efficacy: Duration Of Response (DOR)
DOR is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Efficacy: Progression-Free Survival (PFS)
PFS is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Efficacy: Overall Survival (OS)
OS is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Full Information
NCT ID
NCT03934814
First Posted
April 26, 2019
Last Updated
August 28, 2023
Sponsor
AbbVie
Collaborators
I-Mab Biopharma Co. Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03934814
Brief Title
Study of TJ011133 in Participants With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
April 16, 2019 (Actual)
Primary Completion Date
January 10, 2023 (Actual)
Study Completion Date
January 10, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
I-Mab Biopharma Co. Ltd.
4. Oversight
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.
No
Data Monitoring Committee
No
5. 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.
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 participants 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Lymphoma
Keywords
Solid Tumor, Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1A - TJ011133 Monotherapy
Arm Type
Experimental
Arm Description
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).
Arm Title
Part 1B - Combination therapy of TJ011133 with pembrolizumab
Arm Type
Experimental
Arm Description
TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab.
Arm Title
Part 1C - Combination therapy of TJ011133 with rituximab
Arm Type
Experimental
Arm Description
TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab.
Arm Title
Part 2 - Dose Expansion
Arm Type
Experimental
Arm Description
30 participants (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 participants with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
Intervention Type
Drug
Intervention Name(s)
TJ011133
Intervention Description
TJ011133 will be administered weekly.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab will be administered every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, MabThera
Intervention Description
Rituximab will be administered weekly for 5 doses, then followed by monthly doses.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (DLT)
Description
Part 1A DLT period is 3 weeks, Part 1B DLT period is 3 weeks, Part 1C DLT period is 4 weeks.
Time Frame
21 or 28 days, depending on study part
Title
Incidence and Severity of Adverse Events
Description
The CTCAE criteria will be used to assess adverse events on this trial.
Time Frame
up to 100 days post last dose
Title
Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy
Description
Based on DLT definitions.
Time Frame
21 or 28 days, depending on study part
Title
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
Description
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status.
Time Frame
up to 100 days post last dose
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞)
Description
Area under the curve from time zero to infinity (AUC∞).
Time Frame
up to 100 days post last dose
Title
PK: Area Under the Curve From Time Zero To The Time Of The Last Quantifiable Concentration (AUC0-t)
Description
Area under the curve from time zero to the time of the last quantifiable concentration (AUC0-t).
Time Frame
up to 100 days post last dose
Title
PK: Maximum Observed Concentration (Cmax)
Description
Maximum observed concentration (Cmax).
Time Frame
up to 100 days post last dose
Title
PK: Time of the Maximum Observed Concentration (Tmax)
Description
Time of the maximum observed concentration (Tmax).
Time Frame
up to 100 days post last dose
Title
PK: Terminal Elimination Half-Life (T1/2)
Description
Investigational Product (IP) terminal elimination half-life (T1/2).
Time Frame
up to 100 days post last dose
Title
PK: Clearance (CL)
Description
Investigational Product (IP) Clearance (CL).
Time Frame
up to 100 days post last dose
Title
PK: Volume Of Distribution (Vz)
Description
Investigational Product (IP) volume of distribution (Vz).
Time Frame
up to 100 days post last dose
Title
PK: AUC Over A Dosing Interval (AUCtau)
Description
AUC over a dosing interval (AUCtau).
Time Frame
up to 100 days post last dose
Title
PK: Trough Concentration (Ctrough)
Description
Investigational Product (IP) trough concentration (Ctrough).
Time Frame
up to 100 days post last dose
Title
PK: Volume of Distribution at Steady State (Vss)
Description
Investigational Product (IP) volume of distribution at steady state (Vss).
Time Frame
up to 100 days post last dose
Title
Immunogenicity: Anti-drug antibodies (ADA)
Description
Incidence and concentration of anti-drug antibodies.
Time Frame
up to 100 days post last dose
Title
Efficacy: Best Overall Response (BOR)
Description
BOR is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Time Frame
up to 100 days post last dose
Title
Efficacy: Objective Response Rate (ORR)
Description
ORR is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Time Frame
up to 100 days post last dose
Title
Efficacy: Duration Of Response (DOR)
Description
DOR is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Time Frame
up to 100 days post last dose
Title
Efficacy: Progression-Free Survival (PFS)
Description
PFS is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Time Frame
up to 100 days post last dose
Title
Efficacy: Overall Survival (OS)
Description
OS is determined using Response Elevation Criteria in Solid Tumors (RECIST) 1.1 and immune Response Elevation Criteria in Solid Tumors (iRECIST) guidelines for response criteria for use in trials testing immunotherapeutics for solid tumors and Lugano criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma.
Time Frame
up to 100 days post last dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Part 1: Participants with advanced relapsed/refractory solid tumors and lymphoma.
Part 2 with Rituximab: Participants with diffuse large B-cell lymphoma (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: Participants 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 Response Elevation Criteria in Solid Tumors (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:
Participants with known symptomatic central nervous system tumors or known central nervous system metastases or leptomeningeal disease requiring steroids. Participants who document stable and central nervous system metastases and are off steroids for more than 4 weeks may be enrolled in the study.
Participants with Burkitt's lymphoma, lymphoblastic lymphoma, Richter's transformation, primary effusion lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma.
Participants 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama - Birmingham ID# 233979
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Mayo Clinic /ID# 233546
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Yale School of Medicine /ID# 233748
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Mayo Clinic /ID# 233977
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Horizon Oncology /ID# 234256
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
University of Michigan /ID# 233976
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Cancer Institute/Henry Ford Hospital /ID# 234122
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic /ID# 233305
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey /ID# 232267
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
NYU Langone Health /ID# 233978
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center /ID# 233975
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Seattle Cancer Care Alliance /ID# 233749
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Beijing Cancer Hospital /ID# 241221
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Sun Yat-sen University Cancer Center /ID# 241696
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital) / ID# 242333
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
50011
Country
China
Facility Name
Henan Cancer Hospital /ID# 241670
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Facility Name
HuBei Cancer Hospital /ID# 241673
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Facility Name
The Second Hospital of Dalian Medical University /ID# 241671
City
Dalian
State/Province
Liaoning
ZIP/Postal Code
116027
Country
China
Facility Name
Fudan University Shanghai Cancer Center /ID# 242303
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Name
Tianjin Medical University Cancer Institute & Hospital / ID# 241728
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Name
Zhejiang Cancer Hospital /ID# 241672
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of TJ011133 in Participants With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
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