Lymphoma, Solid Tumor
Conditions
Keywords
Solid Tumor, 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 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.
Interventions
DRUGTJ011133
TJ011133 will be administered weekly.
DRUGPembrolizumab
Pembrolizumab will be administered every 3 weeks.
DRUGRituximab
Rituximab will be administered weekly for 5 doses, then followed by monthly doses.
Sponsors
Merck Sharp & Dohme LLC
I-Mab Biopharma US Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| PK: Terminal Elimination Half-Life (T1/2) | up to 100 days post last dose | Investigational Product (IP) terminal elimination half-life (T1/2). |
| PK: Clearance (CL) | up to 100 days post last dose | Investigational Product (IP) Clearance (CL). |
| PK: Volume Of Distribution (Vz) | up to 100 days post last dose | Investigational Product (IP) volume of distribution (Vz). |
| PK: AUC Over A Dosing Interval (AUCtau) | up to 100 days post last dose | AUC over a dosing interval (AUCtau). |
| PK: Trough Concentration (Ctrough) | up to 100 days post last dose | Investigational Product (IP) trough concentration (Ctrough). |
| 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). |
| 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∞). |
| 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. |
| 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. |
| 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. |
| 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. |
| Immunogenicity: Anti-drug antibodies (ADA) | up to 100 days post last dose | Incidence and concentration of anti-drug antibodies. |
| 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: Time of the Maximum Observed Concentration (Tmax) | up to 100 days post last dose | Time of the maximum observed concentration (Tmax). |
Countries
China, United States
Outcome results
None listed