Study of TJ210001 Administered in Subjects With Relapsed or Refractory Advanced Solid Tumors

NCT04678921 | Completed Phase 1 FDA Drug

• 1 other identifier: TJ210001STM101
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety, tolerability, MTD or MAD, PK, and PD of TJ210001 in subjects with relapsed or refractory advanced solid tumors. Beginning with Dose Level 1, TJ210001 will be given every week starting on Cycle 1 Day 1 (C1D1). The criteria for dose escalation/de-escalation will be based on the Bayesian optimal interval (BOIN) design with sequentially enrolled cohorts. The BOIN design is implemented in a simple way similar to the traditional 3+3 design but is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model-based designs, such as the continual reassessment method (CRM).

Conditions

Solid Tumor; Metastatic Cancer; Advanced Cancer

Keywords

monoclonal antibody; anti-C2aR

Outcome Measures

Primary Outcomes (2)

• Incidence and Severity of Adverse Events

  The CTCAE criteria will be used to assess adverse events on this trial.

  90 days post last dose

• Maximum Tolerated Dose

  Based on DLT Definitions

  21 days

Secondary Outcomes (5)

• Pharmacokinetic Profile

  90 days post last dose

• Pharmacokinetic Profile

  90 days post last dose

• Anti-drug Antibodies (ADA)

  90 days post last dose

• Anti-drug Antibodies (ADA)

  90 days post last dose

• Response Rate

  Up to 2 years

Study Arms (4)

Dose Level 1

EXPERIMENTAL

1mg/kg Q1W

Drug: TJ210001

Dose Level 2

EXPERIMENTAL

3 mg/kg Q1W

Drug: TJ210001

Dose Level 3

EXPERIMENTAL

10mg/kg Q1W

Drug: TJ210001

Dose Level 4

EXPERIMENTAL

15 mg/kg Q1W

Drug: TJ210001

Interventions

TJ210001 DRUG

human anti-C5aR monoclonal antibody

Also known as: MOR210, MOR044254, WBP2191

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, of any race, age ≥ 18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
• Willingness and ability to consent for self to participate in study and the ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
• Histologically confirmed advanced or metastatic cancer in patients who are refractory to or intolerant to all available therapy. Patients who received prior PD-1/PD-L1 checkpoint inhibitor or prior CTLA-4 inhibitor therapy may enroll if they did not experience Grade 3 immune-related toxicity (exceptions may be allowed provided these toxicities have resolved e.g. Grade 3 endocrinopathy that is resolved or clinically stable with hormone replacement therapy). There is no limit to the number of prior treatment regimens;
• At least one measurable lesion as defined by RECIST 1.1;
• Resolution of all acute adverse events resulting from prior cancer therapies to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≤ 1 or baseline (except alopecia or neuropathy);
• Considered by the Investigator to be an appropriate candidate for a Phase 1 clinical study, with a life expectancy of ≥ 12 weeks;
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥ 1500/μL (≥1.5 × 109/L) without growth factor support for 7 days (14 days if on pegfilgrastim) prior to study treatment;
• Platelets ≥ 100,000/μL (≥ 100 ×109/L) without transfusion support within 14 days prior to study treatment;
• Hemoglobin ≥ 9.0 g/dL without transfusion support within 14 days prior to study drug administration (erythropoietin or darbepoetin permitted);
• Adequate renal function and serum creatinine ≤ 1.5 times the ULN or estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault equation4;
• Total serum bilirubin ≤ 1.5 times the ULN, unless patient has documented Gilbert's disease in which case bilirubin ≤ 3.0 times the ULN;
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 times upper limit of normal (ULN) or ≤ 5 times ULN in cases of liver metastases
• Albumin ≥ 3.0 g/dL;

You may not qualify if:

• Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted;
• Current treatment on another therapeutic clinical trial;
• Receipt of systemic anticancer therapy, including investigational agents, within 28 days prior to study treatment (Note: if anticancer therapy was given within 28 days prior to starting study treatment, patients are not excluded if ≥ 5 times the elimination half-life of the drug has elapsed.);
• Prior treatment with C5aR inhibitors;
• Prior T-cell or NK-cell therapy;
• Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment, and must have fully recovered from any such procedure; and no date of surgery (if applicable) or anticipated need for a major surgical procedure planned within the next 6 months (The following are not considered to be major procedures and are permitted up to 14 days prior to study treatment: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, incisional biopsies, and routine dental procedures. Core biopsy and skin biopsy do not require a waiting period prior to dosing.);
• Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as \> 50% of volume of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14 days prior to study treatment - such patients must have recovered adequately from any side effects of such therapy;
• Hypertension defined as blood pressure (BP) systolic \> 150 or diastolic \> 90 mm Hg (Note: Initiation or adjustment of antihypertensive medication prior to study dosing is allowed provided that the average of the three most recent BP readings prior to study enrollment is ≤ 150/90 mm Hg.);
• Ascites, pericardial or pleural effusions that required intervention within 1 month prior to study treatment;
• Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
• Any of the following in the previous 6 months: severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein thrombosis, coronary artery bypass grafting (CABG), or New York Heart Association (NYHA) Class 3 or 4 congestive heart failure;
• Has a diagnosis of immunodeficiency (known active HIV, hepatitis B virus, hepatitis C virus infection) or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;

Sponsors & Collaborators

• I-Mab Biopharma US Limited: lead

Study Sites (4)

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Horizon Oncology Center

Lafayette, Indiana, 47905, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 22, 2020
• Study Start: December 17, 2020
• Primary Completion: November 21, 2022
• Study Completion: November 21, 2022
• Last Updated: December 12, 2022

Record last verified: 2022-12

Locations

US (4)