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

Sponsor
AbbVie (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03934814
Collaborator
I-Mab Biopharma Co. Ltd. (Industry)
98
Enrollment
21
Locations
4
Arms
53
Anticipated Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
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 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
98 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 :
Apr 16, 2019
Anticipated Primary Completion Date :
Sep 15, 2023
Anticipated Study Completion Date :
Sep 15, 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 Names:
  • 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 Names:
  • Rituxan
  • MabThera

    		•
    Experimental: Part 2 - Dose Expansion

    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.

    Drug: TJ011133
    TJ011133 will be administered weekly.

    Drug: Pembrolizumab
    Pembrolizumab will be administered every 3 weeks.
    Other Names:
  • Keytruda

    • Drug: Rituximab
    Rituximab will be administered weekly for 5 doses, then followed by monthly doses.
    Other Names:
  • Rituxan
  • MabThera

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicities (DLT) [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 [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 [21 or 28 days, depending on study part]

      Based on DLT definitions.

    4. Change in Eastern Cooperative Oncology Group (ECOG) Performance Status [up to 100 days post last dose]

      Change in Eastern Cooperative Oncology Group (ECOG) Performance Status.

    Secondary Outcome Measures

    1. Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞) [up to 100 days post last dose]

      Area under the curve from time zero to infinity (AUC∞).

    2. PK: Area Under the Curve From Time Zero To The Time Of The Last Quantifiable Concentration (AUC0-t) [up to 100 days post last dose]

      Area under the curve from time zero to the time of the last quantifiable concentration (AUC0-t).

    3. PK: Maximum Observed Concentration (Cmax) [up to 100 days post last dose]

      Maximum observed concentration (Cmax).

    4. PK: Time of the Maximum Observed Concentration (Tmax) [up to 100 days post last dose]

      Time of the maximum observed concentration (Tmax).

    5. PK: Terminal Elimination Half-Life (T1/2) [up to 100 days post last dose]

      Investigational Product (IP) terminal elimination half-life (T1/2).

    6. PK: Clearance (CL) [up to 100 days post last dose]

      Investigational Product (IP) Clearance (CL).

    7. PK: Volume Of Distribution (Vz) [up to 100 days post last dose]

      Investigational Product (IP) volume of distribution (Vz).

    8. PK: AUC Over A Dosing Interval (AUCtau) [up to 100 days post last dose]

      AUC over a dosing interval (AUCtau).

    9. PK: Trough Concentration (Ctrough) [up to 100 days post last dose]

      Investigational Product (IP) trough concentration (Ctrough).

    10. PK: Volume of Distribution at Steady State (Vss) [up to 100 days post last dose]

      Investigational Product (IP) volume of distribution at steady state (Vss).

    11. Immunogenicity: Anti-drug antibodies (ADA) [up to 100 days post last dose]

      Incidence and concentration of anti-drug antibodies.

    12. Efficacy: Best Overall Response (BOR) [up to 100 days post last dose]

      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.

    13. Efficacy: Objective Response Rate (ORR) [up to 100 days post last dose]

      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.

    14. Efficacy: Duration Of Response (DOR) [up to 100 days post last dose]

      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.

    15. Efficacy: Progression-Free Survival (PFS) [up to 100 days post last dose]

      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.

    16. Efficacy: Overall Survival (OS) [up to 100 days post last dose]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama - Birmingham ID# 233979 Birmingham Alabama United States 35233
    2 Mayo Clinic /ID# 233546 Scottsdale Arizona United States 85259
    3 Yale School of Medicine /ID# 233748 New Haven Connecticut United States 06510
    4 Mayo Clinic /ID# 233977 Jacksonville Florida United States 32224
    5 Horizon Oncology /ID# 234256 Lafayette Indiana United States 47905
    6 University of Michigan /ID# 233976 Ann Arbor Michigan United States 48109
    7 Henry Ford Cancer Institute/Henry Ford Hospital /ID# 234122 Detroit Michigan United States 48202
    8 Mayo Clinic /ID# 233305 Rochester Minnesota United States 55905
    9 Rutgers Cancer Institute of New Jersey /ID# 232267 New Brunswick New Jersey United States 08901
    10 NYU Langone Health /ID# 233978 New York New York United States 10016
    11 Vanderbilt-Ingram Cancer Center /ID# 233975 Nashville Tennessee United States 37203
    12 Seattle Cancer Care Alliance /ID# 233749 Seattle Washington United States 98109
    13 Beijing Cancer Hospital /ID# 241221 Beijing Beijing China 100142
    14 Sun Yat-sen University Cancer Center /ID# 241696 Guangzhou Guangdong China 510000
    15 The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital) / ID# 242333 Shijiazhuang Hebei China 50011
    16 Henan Cancer Hospital /ID# 241670 Zhengzhou Henan China 450003
    17 HuBei Cancer Hospital /ID# 241673 Wuhan Hubei China 430000
    18 The Second Hospital of Dalian Medical University /ID# 241671 Dalian Liaoning China 116027
    19 Fudan University Shanghai Cancer Center /ID# 242303 Shanghai Shanghai China 200000
    20 Tianjin Medical University Cancer Institute & Hospital / ID# 241728 Tianjin Tianjin China 300060
    21 Zhejiang Cancer Hospital /ID# 241672 Hangzhou Zhejiang China 310000

    Sponsors and Collaborators

    • AbbVie
    • I-Mab Biopharma Co. Ltd.

    Investigators

    • Study Director: ABBVIE INC., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03934814
    Other Study ID Numbers:
    • TJ011133EDI101
    • KEYNOTE KN-A21
    First Posted:
    May 2, 2019
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by AbbVie
    Solid Tumor
    Lymphoma
    Additional relevant MeSH terms:
    Lymphoma
    Rituximab
    Pembrolizumab

    Study Results

    No Results Posted as of Aug 24, 2022