Study of RC48-ADC Administered Intravenously to Subjects With HER2-Positive in Advanced Malignant Solid Tumors

A Tolerance, Safety and Pharmacokinetic Ascending Dose Phase I Study of RC48-ADC Administered Intravenously to Subjects With HER2-Positive Malignant in Advanced Malignant Solid Tumors

A tolerance, safety and pharmacokinetic ascending dose phase I Study of RC48-ADC administered intravenously to subjects with HER2-positive malignant in advanced malignant solid tumors.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent form;
• Aged 18-75 years;
• ECOG physical condition is 0 or 1;
• Life expectancy greater than 12 weeks;
• Patients with locally advanced or metastatic malignant solid tumors diagnosed by pathology and refractory to standard of care therapy, or for whom no standard of care therapy is available histology standard of care therapy, or for whom no standard of care therapy is available;
• Human epidermal growth factor receptor 2 (HER2)-positive refers to immunohistochemistry (IHC 2+or 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) <=3.0*upper limit of normal (ULN), or AST and ALT<=5*ULN if liver function abnormalities are due to underlying malignancy;
  • normal serum creatinine;
  • 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% as assessed by echocardiogram.

Exclusion Criteria:

• Current pregnancy or lactation;
• Serologic status reflecting active hepatitis B or C infection;
• 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;
• Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade less than or equal to1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia;
• Prior-treatment with other clinical research anticancer drugs within 28 days before study drug treatment;
• The active infection with clinical significance According to the researcher's judgment,
• Known history of immune deficiency,including HIV-positive or other known acquired or congenital immunodeficiency, or organ transplantation;
• Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or greater than or equal to Class 2 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction unstable angina, or acute coronary syndrome within 6 months prior to enrollment in the study;
• Unwilling or unable to participate in all required study evaluations and procedures;
• The time interval which is from the last chemotherapy or HER2 targeted therapy until the first trial is more than 21 days;
• Patients who had received systemic steroid therapy for a long time (Patients who had received systemic steroid therapy for short time and stopped drug more than 2 weeks could be enrolled);
• Serious complications such as active alimentary tract hemorrhage, intestinal obstruction, enteroparalysis, interstitial pneumonia, pulmonary fibrosis, renal failure, glaucoma and uncontrolled diabetes;
• Uncontrolled primary or metastatic tumor of brain;
• Current peripheral neuropathy of Grade ≥ 2;
• History of nerve or psychiatric disorders.

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; The phase I component has several dose levels of RC48-ADC (0.1mg/kg，0.5 mg/kg, 1.0mg/kg, 1.5mg/kg, 2.0mg/kg, 2.5mg/kg, 3.0mg/kg, 3.5mg/kg and 4.0 mg/kg) and is designed as a traditional dose-escalation study.Dosing interval is once two weeks.	Drug: RC48-ADC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Tolerance Dose (MTD) of RC48-ADC	The dose level in which >= 2 out of 6 patients have dose-limiting toxicity (DLT). The MTD is defined as the previous dose level.	DLT will be evaluated on Day 28 during cycle 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (the drug safety as assessed by NCI-CTCAE v4.0)	The drug safety as assessed by NCI-CTCAE v4.0	up to 2 years

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Publications and helpful links

General Publications

• Xu Y, Wang Y, Gong J, Zhang X, Peng Z, Sheng X, Mao C, Fan Q, Bai Y, Ba Y, Jiang D, Yang F, Qi C, Li J, Wang X, Zhou J, Lu M, Cao Y, Yuan J, Liu D, Wang Z, Fang J, Shen L. Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors. Gastric Cancer. 2021 Jul;24(4):913-925. doi: 10.1007/s10120-021-01168-7. Epub 2021 May 4.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2015
• Primary Completion (Actual): June 27, 2019
• Study Completion (Actual): November 8, 2019

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): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: C002 CANCER

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No