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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04280341
Recruitment Status : Not yet recruiting
First Posted : February 21, 2020
Last Update Posted : February 21, 2020
Sponsor:
Collaborator:
RemeGen
Information provided by (Responsible Party):
Shen Lin, Peking University

Tracking Information
First Submitted Date  ICMJE December 30, 2019
First Posted Date  ICMJE February 21, 2020
Last Update Posted Date February 21, 2020
Estimated Study Start Date  ICMJE March 2020
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2020)
  • DLT(dose-limiting toxicity) [ Time Frame: 28 days ]
    Side effects of drug or treatment that are serious enough to prevent an increase in dose or level of that treatment.
  • ORR [ Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
  • DOR [ Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    The percentage of patients who achieve complete remission(CR) or partial remission (PR) or stable disease(SD) determined by the RECIST v1.1 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2020)
  • PFSR of 6-month and 1-year [ Time Frame: 6 months and 12 months ]
    progression free survival rate
  • CBR(clinical benefit rate) [ Time Frame: up to 2 years ]
    The percentage of patients who have achieved complete response, partial response and stable disease to the therapeutic intervention.
  • adverse events [ Time Frame: 1 year ]
    Safety of participants followed for the duration of hospital stay, an expected average of 1 week
  • ADA [ Time Frame: up to 2 years ]
    anti-drug antibody which can result in treatment failure by blocking the pharmacological function of the drug.
  • NADA [ Time Frame: up to 2 years ]
    neutralizing anti-drug antibody which can result in treatment failure by blocking the pharmacological function of the drug.
  • Cmax [ Time Frame: up to 3 cycles(each cycle is 14 days) ]
    Peak plasma concentration
  • AUC [ Time Frame: up to 3 cycles(each cycle is 14 days) ]
    area under the plasma concentration versus time curve
  • Tmax [ Time Frame: up to 3 cycles(each cycle is 14 days) ]
    Time for peak concentration
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE JS001 in Combination With RC48-ADC in Treatment of HER2-Positive Advanced Malignant Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-Positive Solid Tumors
Intervention  ICMJE Biological: RC48-ADC in combinaton with JS001

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

Study Arms  ICMJE Experimental: RC48-ADC in combinaton with Anti-PD1 Monoclonal Antibody
RC48-ADC(Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate) JS001(Recombinant Humanized Anti-PD1 Monoclonal Antibody)
Intervention: Biological: RC48-ADC in combinaton with JS001
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 19, 2020)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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、CTLA4、LAG3;
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: lin Shen, professor 86-10-88196561 linshenpku@163.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04280341
Other Study ID Numbers  ICMJE RC48-C013
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shen Lin, Peking University
Study Sponsor  ICMJE Peking University
Collaborators  ICMJE RemeGen
Investigators  ICMJE
Principal Investigator: Lin Shen, professor Peking University
PRS Account Peking University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP