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

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

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

Study Overview

• Status: Completed
• Conditions: Lymphoma; Solid Tumor
• Intervention / Treatment: Drug: Pembrolizumab; Drug: TJ011133; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-sen University Cancer Center
  • Hebei
    • Shijiazhuang, Hebei, China, 50011
      • The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital)
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Hubei Cancer Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116027
      • The Second Hospital of Dalian Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Fudan University Shanghai Cancer Center
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Zhejiang Cancer Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama - Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer Institute/Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt-Ingram Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A - TJ011133 Monotherapy; 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).	Drug: TJ011133; TJ011133 will be administered weekly.
Experimental: Part 1B - Combination therapy of TJ011133 with pembrolizumab; TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab.	Drug: Pembrolizumab; Pembrolizumab will be administered every 3 weeks.; Other Names: KEYTRUDA®; Drug: TJ011133; TJ011133 will be administered weekly.
Experimental: Part 1C - Combination therapy of TJ011133 with rituximab; TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab.	Drug: TJ011133; TJ011133 will be administered weekly.; Drug: Rituximab; Rituximab will be administered weekly for 5 doses, then followed by monthly doses.; Other Names: Rituxan; MabThera
Experimental: Part 2 - Dose Expansion; 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.	Drug: Pembrolizumab; Pembrolizumab will be administered every 3 weeks.; Other Names: KEYTRUDA®; Drug: TJ011133; TJ011133 will be administered weekly.; Drug: Rituximab; Rituximab will be administered weekly for 5 doses, then followed by monthly doses.; Other Names: Rituxan; MabThera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy	Based on DLT definitions.	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.	up to 100 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞)	Area under the curve from time zero to infinity (AUC∞).	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).	up to 100 days post last dose
PK: Maximum Observed Concentration (Cmax)	Maximum observed concentration (Cmax).	up to 100 days post last dose
PK: Time of the Maximum Observed Concentration (Tmax)	Time of the maximum observed concentration (Tmax).	up to 100 days post last dose
PK: Terminal Elimination Half-Life (T1/2)	Investigational Product (IP) terminal elimination half-life (T1/2).	up to 100 days post last dose
PK: Clearance (CL)	Investigational Product (IP) Clearance (CL).	up to 100 days post last dose
PK: Volume Of Distribution (Vz)	Investigational Product (IP) volume of distribution (Vz).	up to 100 days post last dose
PK: AUC Over A Dosing Interval (AUCtau)	AUC over a dosing interval (AUCtau).	up to 100 days post last dose
PK: Trough Concentration (Ctrough)	Investigational Product (IP) trough concentration (Ctrough).	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).	up to 100 days post last dose
Immunogenicity: Anti-drug antibodies (ADA)	Incidence and concentration of anti-drug antibodies.	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.	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.	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.	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.	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.	up to 100 days post last dose

Collaborators and Investigators

• Sponsor: I-Mab Biopharma US Limited
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 2, 2019

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Lymphoma; Solid Tumor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Rituximab
• Other Study ID Numbers: TJ011133EDI101; KEYNOTE A21 (Registry Identifier: Merck Sharp & Dohme LLC); MK-3475-A21 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No