RC48-ADC Combined With Radiotherapy in the Treatment of Locally Advanced Solid Tumors With HER2 Expression

NCT ID: NCT05940896

Last Updated: 2023-11-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-29
• Study Completion Date: 2027-02-28

Brief Summary

To evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of Disitamab Vedotin(DV, RC48-ADC) intravenously combined with radiotherapy in the treatment of locally advanced solid tumors with HER2 expression

Detailed Description

This study is a single arm, open, single site clinical study aimed at evaluating the safety, tolerability, pharmacokinetic characteristics, and efficacy of Disitamab Vedotin intravenously combined with radiotherapy in the treatment of locally advanced solid tumors with HER2 expression. Unresectable locally advanced solid tumor patients whose SOC is concurrent chemoradiation but ineligible or refuse to standard chemotherapy should be enrolled.

Conditions

Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

DV is given intravenously once every 2 weeks, (dose escalation plan: 1.0mg/kg, 1.5mg/kg, 2.0mg/kg, 2.5mg/kg). DV will be administered at least 2 times during the treatment, and the final DV dose needs to be completed before the last radiotherapy.

Group Type: EXPERIMENTAL

Disitamab vedotin

Intervention Type: DRUG

Disitamab Vedotin intravenously combined with radiotherapy (concurrent)

Interventions

Disitamab vedotin

Disitamab Vedotin intravenously combined with radiotherapy (concurrent)

Intervention Type: DRUG

Other Intervention Names

RC48-ADC

Eligibility Criteria

Inclusion Criteria

1. Voluntary signed informed consent,

2. Male or female, aged ≥18 years,

3. Predicted survival ≥ 12 weeks;

4. Based on the investigator's evaluation (histopathological classification and clinical staging), patients with locally advanced solid tumors (head and neck squamous cell carcinoma, esophageal carcinoma, urothelium carcinoma, cervical carcinoma, etc), whose SOC is concurrent chemoradiation and cannot be surgically removed, are ineligible or refuse the standard chemotherapy.

5. The subject has not been given any anti-tumor systemic therapy or radiotherapy for locally advanced solid tumors in the past

6. HER2 expression is confirmed by the site: IHC 1+, 2+or 3+;

7. At least one measurable lesion according to RECIST 1.1.

8. ECOG performance status score of 0 or 1;

9. Adequate heart, bone marrow, liver, and kidney functions, which should meet the following standards within 7 days before the study drug is given (based on the normal values of the site) :

Left ventricular ejection fraction ≥ 50%; Hemoglobin ≥ 9g/dL; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L； Platelets ≥ 100 × 10^9/L； Serum total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN； Blood creatinine ≤ 1.5 × ULN or calculate creatinine clearance rate (CrCl) ≥ 50 mL/min according to Cockcroft Fault formula method;

10. Female subjects: should be surgically sterilized, postmenopausal, or agree to use a medically approved contraceptive (such as an intrauterine device, contraceptives, or condoms) during study treatment and within 6 months after the end of study, and their blood pregnancy test must be negative within 7 days prior to study enrollment and they must be non-lactating. Male subjects: should be surgically sterile, or agree to use a medically approved contraceptive during study treatment and within 6 months after the end of study;

11. Willing and able to comply with the schedules of the trial and follow-up procedures.

Exclusion Criteria

1. Received anti-tumor therapy before this study, including radiotherapy, target therapy, immunotherapy, and any anti-tumor clinical studies;

2. The subject was given a major surgery and did not fully recover within 4 weeks prior to the study;

3. Serum virology examination (based on the normal value of the site):

HBsAg or HBcAb test results are positive, while HBV DNA copy is detected as positive; The HCVAb test result is positive (only when the PCR test result for HCV RNA is negative, can it be selected for this study); The HIVAb test result is positive.

4. The subject was given live vaccine within 4 weeks before the study drug is given or planed to receive any vaccine during the study period (except for Covid-19 vaccine);

5. Heart failure≥ 3 grade（NYHA）

6. Serious arteriovenous thrombotic events or cardiovascular and cerebrovascular accidents, such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc., occurred within one year before the study drug is given, except for lacunar cerebral infarction without symptoms or clinical intervention;

7. There are active or progressive infections that require systematic treatment, such as active pulmonary tuberculosis;

8. There are systemic diseases that have not been controlled stably as judged by the investigator, including diabetes, hypertension, cirrhosis, interstitial pneumonia, obstructive pulmonary disease, etc;

9. Active autoimmune diseases that require systematic treatment (such as the use of immunomodulators, corticosteroids, or immunosuppressants) prior to the start of drug administration, allowing for related alternative treatments (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for renal or pituitary dysfunction);

10. Patients with other malignant tumors within 5 years prior to the start of study administration;

11. Previously received other antibody conjugated drug treatments;

12. Those who are known to be allergic to recombinant humanized anti HER2-ADC and components;

13. Pregnant or lactating women;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RemeGen Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jinming Yu, MD

Role: PRINCIPAL_INVESTIGATOR

Shandong Cancer Hospital and Institute

Locations

Shandong Cancer hospital &Institute

Jinan, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianmin Fang, PhD

Role: CONTACT

jianminfang@hotmail.com

86-010-58075561

Na Su, PhD

Role: CONTACT

na.su@remegen.com

86-010-65391479

Facility Contacts

Jinming Yu, Ph.D

Role: primary

Other Identifiers

RC48-C019

Identifier Type: -

Identifier Source: org_study_id