Clinical Trials /

JS001 in Combination With RC48-ADC in Treatment of HER2-Positive Advanced Malignant Solid Tumors

NCT04280341

Description:

This is a non-randomized, open-label, single-arm, multicenter Phase I clinical trial which will evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of RC48-ADC in combinaton with Anti-PD1 Monoclonal Antibody in Treatment of HER2-Positive Advanced Malignant Solid Tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: JS001 in Combination With RC48-ADC in Treatment of HER2-Positive Advanced Malignant Solid Tumors
  • Official Title: A Phase I, Open-label, Dose Escalation Clinical Trial to Assess the Safety, Efficacy, Tolerability and Pharmacokinetics of the Recombinant Humanized Anti-PD1 Monoclonal Antiody (JS001) in Combination With Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate (RC48-ADC) in Treatment of HER2-Positive Advanced Malignant Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: RC48-C013
  • NCT ID: NCT04280341

Conditions

  • HER2-Positive Solid Tumors

Interventions

DrugSynonymsArms
RC48-ADC in combinaton with JS001RC48-ADC in combinaton with Anti-PD1 Monoclonal Antibody

Purpose

This is a non-randomized, open-label, single-arm, multicenter Phase I clinical trial which will evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of RC48-ADC in combinaton with Anti-PD1 Monoclonal Antibody in Treatment of HER2-Positive Advanced Malignant Solid Tumors.

Detailed Description

      The study has 2 parts which include dose escalation phase and dose extension phase.

      Dose escalation will use a 3+3 design and will enroll cohorts of 3-6 patients with
      HER2-Positive Advanced Malignant Solid Tumors sequentially at escalating doses of 2.0mg/kg
      and 2.5mg/kg to RC48-ADC and JS001 is fixed dose of 3.0mg/mg . Escalation will continue until
      identification of a MTD.

      Dose of phase II and extenstion stage which based-results of escalation phase will be
      recommend.
    

Trial Arms

NameTypeDescriptionInterventions
RC48-ADC in combinaton with Anti-PD1 Monoclonal AntibodyExperimentalRC48-ADC(Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate) JS001(Recombinant Humanized Anti-PD1 Monoclonal Antibody)
  • RC48-ADC in combinaton with JS001

Eligibility Criteria

        Inclusion Criteria:

          -  Willing to sign the informed consent form;

          -  ≥18 years old;

          -  Diagnosed histologically or cytologically with local advanced or metastatic
             HER2-positive malignant solid cancer( indicating that IHC result is 2+,3+or1+ ) and
             under one of following situations: standard treatment-refractory (disease progression
             or no response), treatment-resistant, unable to receive treatment, or the standard
             treatment is unavailable;

          -  Having measurable or evaluable lesions according to RECIST 1.1;

          -  Having an ECOG performance status score of 0 or 1;

          -  Echocardiographic LVEF (left ventricular ejection fraction) ≥ 50%.

          -  NYHA CLAS 0-1;

          -  Having sufficient bone marrow, liver and kidney functions (based on the normal value
             of the clinical trial site) within 7 days before erollment: Absolute neutrophil count
             (ANC) ≥ 1.5×109/L,Platelets ≥ 100×109/L, hemoglobin≥ 9.0 g/dL;Total serum bilirubin ≤
             1.5×upper limit of normal (ULN);Without liver metastasis, ALT, AST or ALP ≤ 2.5×ULN;
             With liver metastasis, ALT, AST or ALP ≤ 5×ULN;Serum creatinine clearance rate ≥ 60
             mL/min(Cockcroft-Gault formula);INR International Normalized Ratio ≤ 1.5 × ULN, APTT ≤
             1.5 × ULN;

          -  With an expected survival of more than 3 months;

          -  Male or female patients of childbearing potential must agree to use effective methods
             of contraception (such as double-barrier contraceptive methods, condoms, oral or
             injectable contraceptives and intrauterine devices) during the study period and within
             24 weeks after the last dosing;

        Exclusion Criteria:

          -  Known active uncontrolled or symptomatic CNS metastases, as indicated by clinical
             symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis,
             leptomeningeal disease and/or progressive growth. Patients with a history of CNS
             metastases or cord compression are eligible if they have been definitively treated and
             are clinically stable o before the first dose of RC48-ADC.

          -  Prior treatment with HER2 targeted therapy while LVEF decline <45% or absolute value
             of LVEF decline >15%;

          -  Participation in any other studies within 4 weeks before study entry and/or during
             participation in the active treatment phase of the trial.

          -  Radical operation within 3 weeks before study entry but not include diagnostic
             puncture or peripheral vascular assess replacement ;

          -  Radical radiation therapy within 3 months before study entry; Patient of Palliative
             radiotherapy is eligible into this study if <30 % Radiation area of bone marrow;

          -  Patients who underwent checkpoint inhibitor or tumor vaccines include not limited
             PD-1、 PD-1、PD-L1、CTLA4LAG3;

          -  Patient has had systemic steroid therapy (≥10 mg/day of prednisone or physiologic
             replacement doses of hydrocortisone, or its equivalent) or immunosuppressive
             medication within 14 days prior to the first dose of study.

          -  Live vaccines within 28 days prior to the first dose of study and during trial
             treatment.

          -  Patient has an active autoimmune disease or a documented history of autoimmune disease
             (but not limited In terstitial lung Disease, uveitis, SLE, etal). Patients with
             vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients
             that require inhaled steroids or local steroid injections would not be excluded from
             the study. Patients with vitiligo or psoriasis that is stable on hormone replacement
             will not be excluded from the study.

          -  Active and clinically significant bacterial, fungal or viral infection including
             hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or
             acquired immunodeficiency syndrome (AIDS)-related illness.

          -  Patients have uncontrollable systemic disease which including diabetes, hypertendion,
             pulmonary fibrosis, etal.

          -  The toxicity of previous anti-cancer therapy has not returned to 0 or 1 level as
             specified in CTCAE v4.0 (except for hair loss);

          -  Patient has a history of allogeneic HSCT or organ transplation before study entry;

          -  Patients with hypersensitivity or delayed hypersensitivity reactions to certain
             components of RC48-ADC or similar drugs;

          -  Patients with symptomatic include but not limited ascites or pleural effusion and
             mental disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:DLT(dose-limiting toxicity)
Time Frame:28 days
Safety Issue:
Description:Side effects of drug or treatment that are serious enough to prevent an increase in dose or level of that treatment.

Secondary Outcome Measures

Measure:PFSR of 6-month and 1-year
Time Frame:6 months and 12 months
Safety Issue:
Description:progression free survival rate
Measure:CBR(clinical benefit rate)
Time Frame:up to 2 years
Safety Issue:
Description:The percentage of patients who have achieved complete response, partial response and stable disease to the therapeutic intervention.
Measure:adverse events
Time Frame:1 year
Safety Issue:
Description:Safety of participants followed for the duration of hospital stay, an expected average of 1 week
Measure:ADA
Time Frame:up to 2 years
Safety Issue:
Description:anti-drug antibody which can result in treatment failure by blocking the pharmacological function of the drug.
Measure:NADA
Time Frame:up to 2 years
Safety Issue:
Description:neutralizing anti-drug antibody which can result in treatment failure by blocking the pharmacological function of the drug.
Measure:Cmax
Time Frame:up to 3 cycles(each cycle is 14 days)
Safety Issue:
Description:Peak plasma concentration
Measure:AUC
Time Frame:up to 3 cycles(each cycle is 14 days)
Safety Issue:
Description:area under the plasma concentration versus time curve
Measure:Tmax
Time Frame:up to 3 cycles(each cycle is 14 days)
Safety Issue:
Description:Time for peak concentration

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Peking University

Trial Keywords

  • RC48-ADC
  • JS001
  • HER2 positive solid Tumor

Last Updated

February 19, 2020