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

I-Mab Biopharma US Limited98 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor Lymphoma

Interventions

TJ011133DRUG

TJ011133 will be administered weekly.

PembrolizumabDRUG

Pembrolizumab will be administered every 3 weeks.

RituximabDRUG

Rituximab will be administered weekly for 5 doses, then followed by monthly doses.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (21)

University of Alabama - Birmingham

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: up to 100 days post last dose

Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy

Based on DLT definitions.

Time frame: 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.

Time frame: up to 100 days post last dose

Secondary Outcomes

Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞)

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

Time frame: 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).

Time frame: up to 100 days post last dose

PK: Maximum Observed Concentration (Cmax)

Maximum observed concentration (Cmax).

Time frame: up to 100 days post last dose

PK: Time of the Maximum Observed Concentration (Tmax)

Data from ClinicalTrials.gov

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Mayo Clinic

Scottsdale, Arizona, United States

Yale School of Medicine

New Haven, Connecticut, United States

Mayo Clinic

Jacksonville, Florida, United States

Horizon Oncology

Lafayette, Indiana, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Cancer Institute/Henry Ford Hospital

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

NYU Langone Health

New York, New York, United States

...and 11 more locations

Time of the maximum observed concentration (Tmax).

Time frame: up to 100 days post last dose

PK: Terminal Elimination Half-Life (T1/2)

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

Time frame: up to 100 days post last dose

PK: Clearance (CL)

Investigational Product (IP) Clearance (CL).

Time frame: up to 100 days post last dose

PK: Volume Of Distribution (Vz)

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

Time frame: up to 100 days post last dose

PK: AUC Over A Dosing Interval (AUCtau)

AUC over a dosing interval (AUCtau).

Time frame: up to 100 days post last dose

PK: Trough Concentration (Ctrough)

Investigational Product (IP) trough concentration (Ctrough).

Time frame: 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).

Time frame: up to 100 days post last dose

Immunogenicity: Anti-drug antibodies (ADA)

Incidence and concentration of anti-drug antibodies.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: up to 100 days post last dose