Clinical trial NCT03934814: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lymphoma
Keywords: Solid Tumor
Lymphoma
Lead sponsor: I-Mab Biopharma US Limited
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-05-02
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: 21 or 28 days, depending on study part
measure: Incidence and Severity of Adverse Events
timeFrame: up to 100 days post last dose
measure: Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy
timeFrame: 21 or 28 days, depending on study part
measure: Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: up to 100 days post last dose
Secondary outcomes:
measure: Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞)
timeFrame: up to 100 days post last dose
measure: PK: Area Under the Curve From Time Zero To The Time Of The Last Quantifiable Concentration (AUC0-t)
timeFrame: up to 100 days post last dose
measure: PK: Maximum Observed Concentration (Cmax)
timeFrame: up to 100 days post last dose
measure: PK: Time of the Maximum Observed Concentration (Tmax)
timeFrame: up to 100 days post last dose
measure: PK: Terminal Elimination Half-Life (T1/2)
timeFrame: up to 100 days post last dose
measure: PK: Clearance (CL)
timeFrame: up to 100 days post last dose
measure: PK: Volume Of Distribution (Vz)
timeFrame: up to 100 days post last dose
measure: PK: AUC Over A Dosing Interval (AUCtau)
timeFrame: up to 100 days post last dose
measure: PK: Trough Concentration (Ctrough)
timeFrame: up to 100 days post last dose
measure: PK: Volume of Distribution at Steady State (Vss)
timeFrame: up to 100 days post last dose
measure: Immunogenicity: Anti-drug antibodies (ADA)
timeFrame: up to 100 days post last dose
measure: Efficacy: Best Overall Response (BOR)
timeFrame: up to 100 days post last dose
measure: Efficacy: Objective Response Rate (ORR)
timeFrame: up to 100 days post last dose
measure: Efficacy: Duration Of Response (DOR)
timeFrame: up to 100 days post last dose
measure: Efficacy: Progression-Free Survival (PFS)
timeFrame: up to 100 days post last dose
measure: Efficacy: Overall Survival (OS)
timeFrame: up to 100 days post last dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Lafayette
country: United States
facility: Horizon Oncology
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Cancer Institute/Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shijiazhuang
country: China
facility: The Fourth Hpspital of Hebei Medical University(Hebei Cancer Hospital)
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: HuBei Cancer Hospital
state: Hubei
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: