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

Lymphoma Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03934814
• Other study ID #: TJ011133EDI101
• Secondary ID: KEYNOTE KN-A21
• Status: Completed
• Phase: Phase 1
• Start date: April 16, 2019
• Est. completion date: January 10, 2023

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: January 10, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 SIRPa 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.

Related Conditions & MeSH terms

• Lymphoma
• Solid Tumor

Intervention

Drug:
• TJ011133
TJ011133 will be administered weekly.
• Pembrolizumab
Pembrolizumab will be administered every 3 weeks.
• Rituximab
Rituximab will be administered weekly for 5 doses, then followed by monthly doses.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital /ID# 241221	Beijing	Beijing
China	The Second Hospital of Dalian Medical University /ID# 241671	Dalian	Liaoning
China	Sun Yat-sen University Cancer Center /ID# 241696	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital /ID# 241672	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center /ID# 242303	Shanghai	Shanghai
China	The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital) / ID# 242333	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute & Hospital / ID# 241728	Tianjin	Tianjin
China	HuBei Cancer Hospital /ID# 241673	Wuhan	Hubei
China	Henan Cancer Hospital /ID# 241670	Zhengzhou	Henan
United States	University of Michigan /ID# 233976	Ann Arbor	Michigan
United States	University of Alabama - Birmingham ID# 233979	Birmingham	Alabama
United States	Henry Ford Cancer Institute/Henry Ford Hospital /ID# 234122	Detroit	Michigan
United States	Mayo Clinic /ID# 233977	Jacksonville	Florida
United States	Horizon Oncology /ID# 234256	Lafayette	Indiana
United States	Vanderbilt-Ingram Cancer Center /ID# 233975	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey /ID# 232267	New Brunswick	New Jersey
United States	Yale School of Medicine /ID# 233748	New Haven	Connecticut
United States	NYU Langone Health /ID# 233978	New York	New York
United States	Mayo Clinic /ID# 233305	Rochester	Minnesota
United States	Mayo Clinic /ID# 233546	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance /ID# 233749	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	I-Mab Biopharma Co. Ltd.

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy	Based on DLT definitions.	21 or 28 days, depending on study part
Primary	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	Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC8)	Area under the curve from time zero to infinity (AUC8).	up to 100 days post last dose
Secondary	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
Secondary	PK: Maximum Observed Concentration (Cmax)	Maximum observed concentration (Cmax).	up to 100 days post last dose
Secondary	PK: Time of the Maximum Observed Concentration (Tmax)	Time of the maximum observed concentration (Tmax).	up to 100 days post last dose
Secondary	PK: Terminal Elimination Half-Life (T1/2)	Investigational Product (IP) terminal elimination half-life (T1/2).	up to 100 days post last dose
Secondary	PK: Clearance (CL)	Investigational Product (IP) Clearance (CL).	up to 100 days post last dose
Secondary	PK: Volume Of Distribution (Vz)	Investigational Product (IP) volume of distribution (Vz).	up to 100 days post last dose
Secondary	PK: AUC Over A Dosing Interval (AUCtau)	AUC over a dosing interval (AUCtau).	up to 100 days post last dose
Secondary	PK: Trough Concentration (Ctrough)	Investigational Product (IP) trough concentration (Ctrough).	up to 100 days post last dose
Secondary	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
Secondary	Immunogenicity: Anti-drug antibodies (ADA)	Incidence and concentration of anti-drug antibodies.	up to 100 days post last dose
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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