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

I-Mab Biopharma

Status and phase: Completed; Phase 1

Conditions: Solid Tumor; Lymphoma

Treatments: Drug: Rituximab; Drug: Pembrolizumab; Drug: TJ011133

Study type: Interventional

Funder types: Industry

Identifiers

NCT03934814

TJ011133EDI101

KEYNOTE A21 (Registry Identifier)

MK-3475-A21 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 98 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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98 participants in 4 patient groups

Part 1A - TJ011133 Monotherapy

Experimental group

Description:

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).

Treatment:

Drug: TJ011133

Part 1B - Combination therapy of TJ011133 with pembrolizumab

Experimental group

Description:

TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab.

Treatment:

Drug: TJ011133

Drug: Pembrolizumab

Part 1C - Combination therapy of TJ011133 with rituximab

Experimental group

Description:

TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab.

Treatment:

Drug: TJ011133

Drug: Rituximab

Part 2 - Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: TJ011133

Drug: Pembrolizumab

Drug: Rituximab