Clinical Trials /

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

NCT04678921

Description:

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).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of TJ210001 Administered in Subjects With Relapsed or Refractory Advanced Solid Tumors
  • Official Title: A Phase 1 Study of TJ210001 Administered in Subjects With Relapsed or Refractory Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TJ210001STM101
  • NCT ID: NCT04678921

Conditions

  • Solid Tumor
  • Metastatic Cancer
  • Advanced Cancer

Interventions

DrugSynonymsArms
TJ210001MOR210, MOR044254, WBP2191Dose Level 1

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Dose Level 1Experimental1mg/kg Q1W
  • TJ210001
Dose Level 2Experimental3 mg/kg Q1W
  • TJ210001
Dose Level 3Experimental10mg/kg Q1W
  • TJ210001
Dose Level 4Experimental15 mg/kg Q1W
  • TJ210001

Eligibility Criteria

        Inclusion Criteria:

          1. Males or females, of any race, age ≥ 18 years;

          2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;

          3. 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;

          4. 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;

          5. At least one measurable lesion as defined by RECIST 1.1;

          6. 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);

          7. Considered by the Investigator to be an appropriate candidate for a Phase 1 clinical
             study, with a life expectancy of ≥ 12 weeks;

          8. Adequate organ function as defined by the following criteria:

               1. 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;

               2. Platelets ≥ 100,000/μL (≥ 100 ×109/L) without transfusion support within 14 days
                  prior to study treatment;

               3. Hemoglobin ≥ 9.0 g/dL without transfusion support within 14 days prior to study
                  drug administration (erythropoietin or darbepoetin permitted);

               4. Adequate renal function and serum creatinine ≤ 1.5 times the ULN or estimated
                  creatinine clearance ≥ 30 mL/min by Cockcroft-Gault equation4;

               5. Total serum bilirubin ≤ 1.5 times the ULN, unless patient has documented
                  Gilbert's disease in which case bilirubin ≤ 3.0 times the ULN;

               6. 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

               7. Albumin ≥ 3.0 g/dL;

               8. Prothrombin Time (PT) ≤ 1.5 times the ULN, or 11 to 15 seconds in the absence of
                  a normal range; partial thromboplastin time (PTT) or activated partial
                  thromboplastin time (aPTT) ≤ 1.5 times the ULN; and international normalized
                  ratio (INR) ≤ 1.5 times the ULN unless the subject is receiving anticoagulant
                  therapy.

          9. Subject with a QT interval corrected for heart rate using Fridericia's formula (QTcF)
             and/or QT interval corrected for heart rate using Bazett's formula of < 470 msec for
             both males and females;

         10. A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1
             therapy;

         11. Women of childbearing potential (WOCBP) must:

               1. Agree to use at least 2 effective contraceptive methods (1 highly effective
                  method in combination with a barrier method; oral, injectable, or implantable
                  hormonal contraceptive; tubal ligation; intra-uterine device; barrier
                  contraceptive with spermicide; or vasectomized partner), one of which must be
                  barrier, from signing the ICF, throughout the study, and for up to 12 weeks
                  following the last dose of TJ210001;

               2. Have a negative serum pregnancy test (sensitive of at least 25 mIU/ml) at
                  screening; and have a negative serum or urine pregnancy test (Investigator's
                  discretion) within 72 hours prior to Cycle 1 Day -1 of study treatment (note that
                  the screening serum pregnancy test can be used as the test prior to Day -1 study
                  treatment if it is performed within the prior 72 hours);

               3. Avoid conceiving for 12 weeks after the last dose of TJ210001;

               4. Avoid donation of ova from signing the ICF until 12 weeks after the last dose of
                  TJ210001;

               5. Agree to ongoing urine pregnancy testing, if clinically indicated, during the
                  course of the study.

         12. Males must agree to use a condom (a latex condom is recommended) during sexual contact
             with a pregnant female or a female of childbearing potential and will avoid donation
             of sperm or having a female partner conceive from the time of signing the ICF, while
             participating in the study, during dose interruptions, and for at least 12 weeks after
             the last dose of study treatment, even if he has undergone a successful vasectomy.

        Exclusion Criteria:

          1. 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;

          2. Current treatment on another therapeutic clinical trial;

          3. 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.);

          4. Prior treatment with C5aR inhibitors;

          5. Prior T-cell or NK-cell therapy;

          6. 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.);

          7. 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;

          8. 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.);

          9. Ascites, pericardial or pleural effusions that required intervention within 1 month
             prior to study treatment;

         10. 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;

         11. 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;

         12. 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;
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and Severity of Adverse Events
Time Frame:90 days post last dose
Safety Issue:
Description:The CTCAE criteria will be used to assess adverse events on this trial.

Secondary Outcome Measures

Measure:Pharmacokinetic Profile
Time Frame:90 days post last dose
Safety Issue:
Description:Cmax
Measure:Pharmacokinetic Profile
Time Frame:90 days post last dose
Safety Issue:
Description:AUC
Measure:Anti-drug Antibodies (ADA)
Time Frame:90 days post last dose
Safety Issue:
Description:Incidence of anti-drug antibodies
Measure:Anti-drug Antibodies (ADA)
Time Frame:90 days post last dose
Safety Issue:
Description:Concentration of anti-drug antibodies
Measure:Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description:RECIST 1.1 will be used to assess response rate on this trial.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:I-Mab Biopharma Co. Ltd.

Trial Keywords

  • monoclonal antibody
  • anti-C2aR

Last Updated

December 22, 2020