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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Solid Tumor, Lymphoma

Intervention / Treatment
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* Drug: TJ011133
* Drug: Pembrolizumab
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A - TJ011133 Monotherapy<br>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<br>* TJ011133 will be administered weekly.<br>|
| Experimental: Part 1B - Combination therapy of TJ011133 with pembrolizumab<br>TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab. | Drug: TJ011133<br>* TJ011133 will be administered weekly.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered every 3 weeks.<br>* Other names: Keytruda;|
| Experimental: Part 1C - Combination therapy of TJ011133 with rituximab<br>TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab. | Drug: TJ011133<br>* TJ011133 will be administered weekly.<br>Drug: Rituximab<br>* Rituximab will be administered weekly for 5 doses, then followed by monthly doses.<br>* Other names: MabThera;|
| Experimental: Part 2 - Dose Expansion<br>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<br>* TJ011133 will be administered weekly.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered every 3 weeks.<br>* Other names: Keytruda;Drug: Rituximab<br>* Rituximab will be administered weekly for 5 doses, then followed by monthly doses.<br>* Other names: MabThera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 21 or 28 days, depending on study part | 
| Incidence and Severity of Adverse Events | The CTCAE criteria will be used to assess adverse events on this trial. | up to 100 days post last dose | 
| Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy | Based on DLT definitions. | 21 or 28 days, depending on study part | 
| Change in Eastern Cooperative Oncology Group (ECOG) Performance Status | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status. | up to 100 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞) | Area under the curve from time zero to infinity (AUC∞). | up to 100 days post last dose | 
| 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). | up to 100 days post last dose | 
| PK: Maximum Observed Concentration (Cmax) | Maximum observed concentration (Cmax). | up to 100 days post last dose | 
| PK: Time of the Maximum Observed Concentration (Tmax) | Time of the maximum observed concentration (Tmax). | up to 100 days post last dose | 
| PK: Terminal Elimination Half-Life (T1/2) | Investigational Product (IP) terminal elimination half-life (T1/2). | up to 100 days post last dose | 
| PK: Clearance (CL) | Investigational Product (IP) Clearance (CL). | up to 100 days post last dose | 
| PK: Volume Of Distribution (Vz) | Investigational Product (IP) volume of distribution (Vz). | up to 100 days post last dose | 
| PK: AUC Over A Dosing Interval (AUCtau) | AUC over a dosing interval (AUCtau). | up to 100 days post last dose | 
| PK: Trough Concentration (Ctrough) | Investigational Product (IP) trough concentration (Ctrough). | up to 100 days post last dose | 
| PK: Volume of Distribution at Steady State (Vss) | Investigational Product (IP) volume of distribution at steady state (Vss). | up to 100 days post last dose | 
| Immunogenicity: Anti-drug antibodies (ADA) | Incidence and concentration of anti-drug antibodies. | up to 100 days post last dose | 
| 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. | up to 100 days post last dose | 
| 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. | up to 100 days post last dose | 
| 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. | up to 100 days post last dose | 
| 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. | up to 100 days post last dose | 
| 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. | up to 100 days post last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor, Lymphoma