A Study of RC48-ADC in Subjects With HER2-Positive Advanced Malignant Solid Tumors

A Phase I Study to Evaluate the Safety,Tolerability and Pharmacokinetics of RC48-ADC for Injection in Subjects With Advanced Malignant Solid Tumors With HER2-positive

A Phase I Study to Evaluate the Safety,Tolerability and Pharmacokinetics of RC48-ADC for Injection in Subjects With Advanced Malignant Solid Tumors With HER2-positive

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: RC48-ADC

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent form;
• Aged 18-65 years;
• ECOG physical condition is 0 or 1;
• Life expectancy greater than 12 weeks;
• Diagnosed with histologically or cytologically-confirmed, standard treatment is ineffective (disease progresses after treatment) or HER2-positive, locally advanced or metastatic malignant solid tumor patients who cannot tolerate standard therapy, cannot receive or do not have standard therapy;
• Human epidermal growth factor receptor 2 (HER2)-positive as measured either by immunohistochemistry (IHC 2+ and by fluorescence in situ hybridization (FISH) or by immunohistochemistry (3+);
• Patients with measurable and appreciable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1);

• Adequate organ function as defined by the following criteria:

  • absolute neutrophil count(ANC) >= 1.5 x 10(9)/L;
  • platelets>=100*10(9)/L;
  • Total serum bilirubin <=1.5*ULN;
  • serum aspartate transaminase (AST) and serum alanine transaminase (ALT) <=2.5*upper limit of normal (ULN), or AST and ALT<=5*ULN with hepatic metastasis;
  • Serum creatinine clearance rate >=45ml/min;
  • international normalized ratio (INR) and activated partial thromboplastin time (APTT) must be less than or equal to 1.5 times the upper limit of the normal range (ULN);
• Women of child-bearing potential and men must agree to use adequate contraception (e.g. condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete sexual abstinence, or sterilized partner) prior to study entry and during the period of therapy and for 30 days after the last dose of study drug;
• Left ventricular ejection fraction (LVEF) >= 50%.

Exclusion Criteria:

• Current pregnancy or lactation;
• Received anti-tumor treatment 4 weeks before study administration, including chemotherapy, radiotherapy, hormone therapy, biological therapy or immunotherapy, except the following: Gonadotropin-releasing hormone (GnRH) antagonistic therapy for prostate cancer and Hormone replacement therapy;
• Major surgery within 4 weeks of first dose of study drug and not fully recovered;
• Receiving palliative radiation therapy for bone metastases if administered <= 2 weeks prior to first study treatment;
• Toxicity of previous anti-tumor treatment has not recovered to CTCAE [version 4.0] 0-1 (with exception of alopecia);
• Participated in other clinical drug studies within 4 weeks;
• Hypersensitivity or delayed allergic reaction to certain components of RC48-ADC or similar drugs;
• According to the judgment of the investigator, a clinically significant active infection;
• A history of immunodeficiency, including a positive HIV test, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
• Uncontrollable systemic diseases including diabetes, hypertension, lung Fibrosis, acute lung disease, interstitial lung disease, etc.;
• Congestive heart failure with grade 2 or higher (including grade 2) by the New York Institute of Cardiology (NYHA) of the United States in the history of diseases such as acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months before enrollment;
• Insufficient adherence to participate in this clinical study;
• Treated with Herceptin (Trastuzumab) within 60 days before the trial;
• Have received systemic steroid therapy for a long time ( short-term users who discontinue medication> 2 weeks can be selected);
• Uncontrolled primary or metastatic tumor of brain;
• Peripheral neuropathy with grade>= 2;
• People with a history of mental illness that is difficult to control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC48-ADC; Participants will be allocated to one of the following dose groups: 0.5, 1.0, 1.5, 2.0 and 2.5 mg/kg, and receive a treatment of RC48-ADC followed by 28 days of dose limited toxicity (DLT) observation period.	Drug: RC48-ADC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximal tolerance dose (MTD) of RC48-ADC	Maximum-tolerated dose (MTD) was defined as the highest dose level at which no more than one of six patients experienced DLT during the DLT assessment window.	DLT will be evaluated on 28 days of observation period
AEs	The drug safety was assessed by investigator(s) according to NCI-CTCAE v4.0	Estimated 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Observed Plasma Concentration	Estimated 2 years
AUC	Area Under Curve	Estimated 2 years
Tmax	Time for Cmax	Estimated 2 years

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): July 15, 2020

Study Registration Dates

• First Submitted: August 20, 2016
• First Submitted That Met QC Criteria: August 25, 2016
• First Posted (Estimate): August 26, 2016

Study Record Updates

• Last Update Posted (Actual): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 28, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: C001 CANCER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided