Study of TJ011133 in Participants With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
- Conditions
- Solid TumorLymphoma
- Interventions
- Registration Number
- NCT03934814
- Lead Sponsor
- I-Mab Biopharma US Limited
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1A - TJ011133 Monotherapy TJ011133 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). Part 1B - Combination therapy of TJ011133 with pembrolizumab TJ011133 TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab. Part 1C - Combination therapy of TJ011133 with rituximab TJ011133 TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab. Part 1B - Combination therapy of TJ011133 with pembrolizumab Pembrolizumab TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab. Part 2 - Dose Expansion TJ011133 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. Part 1C - Combination therapy of TJ011133 with rituximab Rituximab TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab. Part 2 - Dose Expansion 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. Part 2 - Dose Expansion Pembrolizumab 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.
- Primary Outcome Measures
Name Time Method 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.
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.
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.
Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy 21 or 28 days, depending on study part Based on DLT definitions.
- Secondary Outcome Measures
Name Time Method 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).
PK: Maximum Observed Concentration (Cmax) up to 100 days post last dose Maximum observed concentration (Cmax).
PK: Trough Concentration (Ctrough) up to 100 days post last dose Investigational Product (IP) trough concentration (Ctrough).
PK: Volume Of Distribution (Vz) up to 100 days post last dose Investigational Product (IP) volume of distribution (Vz).
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.
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.
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∞).
PK: Terminal Elimination Half-Life (T1/2) up to 100 days post last dose Investigational Product (IP) terminal elimination half-life (T1/2).
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).
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.
PK: Time of the Maximum Observed Concentration (Tmax) up to 100 days post last dose Time of the maximum observed concentration (Tmax).
PK: Clearance (CL) up to 100 days post last dose Investigational Product (IP) Clearance (CL).
PK: AUC Over A Dosing Interval (AUCtau) up to 100 days post last dose AUC over a dosing interval (AUCtau).
Immunogenicity: Anti-drug antibodies (ADA) up to 100 days post last dose Incidence and concentration of anti-drug antibodies.
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.
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.
Trial Locations
- Locations (19)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
NYU Langone Health
🇺🇸New York, New York, United States
Henry Ford Cancer Institute/Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital)
🇨🇳Shijiazhuang, Hebei, China
HuBei Cancer Hospital
🇨🇳Wuhan, Hubei, China
The Second Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Horizon Oncology
🇺🇸Lafayette, Indiana, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States