Description:
The purpose of this study is to assess the safety and tolerability of TJ011133 in
participants with solid tumors and lymphoma.
Title
- Brief Title: Study of TJ011133 in Participants With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
TJ011133EDI101
- SECONDARY ID:
KEYNOTE KN-A21
- NCT ID:
NCT03934814
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| TJ011133 | | Part 1A - TJ011133 Monotherapy |
| Pembrolizumab | Keytruda | Part 1B - Combination therapy of TJ011133 with pembrolizumab |
| Rituximab | Rituxan, MabThera | Part 1C - Combination therapy of TJ011133 with rituximab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1A - TJ011133 Monotherapy | Experimental | 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 | Experimental | TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab. | |
| Part 1C - Combination therapy of TJ011133 with rituximab | Experimental | TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab. | |
| Part 2 - Dose Expansion | Experimental | 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. | - TJ011133
- Pembrolizumab
- Rituximab
|
Eligibility Criteria
Inclusion Criteria:
- Part 1: Participants with advanced relapsed/refractory solid tumors and lymphoma.
- Part 2 with Rituximab: Participants with 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 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Limiting Toxicities (DLT) |
| Time Frame: | 21 or 28 days, depending on study part |
| Safety Issue: | |
| Description: | Part 1A DLT period is 3 weeks, Part 1B DLT period is 3 weeks, Part 1C DLT period is 4 weeks. |
Secondary Outcome Measures
| Measure: | Pharmacokinetic Parameters: Tmax |
| Time Frame: | up to 100 days post last dose |
| Safety Issue: | |
| Description: | Time of peak concentration (Tmax). |
| Measure: | Pharmacokinetic Parameters: Cmax |
| Time Frame: | up to 100 days post last dose |
| Safety Issue: | |
| Description: | Maximal concentration (Cmax). |
| Measure: | Pharmacokinetic Parameters: T1/2 |
| Time Frame: | up to 100 days post last dose |
| Safety Issue: | |
| Description: | Investigational Product (IP) half-life (T1/2). |
| Measure: | Pharmacokinetic Parameters: CL |
| Time Frame: | up to 100 days post last dose |
| Safety Issue: | |
| Description: | Investigational Product (IP) Clearance (CL). |
| Measure: | Pharmacokinetic (PK) Parameters: AUC∞ |
| Time Frame: | up to 100 days post last dose |
| Safety Issue: | |
| Description: | Area under the curve from time zero extrapolated to infinity (AUC∞). |
| Measure: | Anti-drug antibodies (ADA) |
| Time Frame: | up to 100 days post last dose |
| Safety Issue: | |
| Description: | Incidence and concentration of anti-drug antibodies. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
Last Updated
June 30, 2021
