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

Solid Tumor Clinical Trial

Official title:

Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of Disitamab Vedotin Intravenously Combined With Radiotherapy in the Treatment of Locally Advanced Solid Tumors With HER2 Expression Phase 1 Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05940896
• Other study ID #: RC48-C019
• Status: Recruiting
• Phase: Phase 1
• Start date: June 29, 2023
• Est. completion date: February 28, 2027

Study information

• Verified date: November 2023
• Source: RemeGen Co., Ltd.
• Contact: Jianmin Fang, PhD
• Phone: 86-010-58075561
• Email: jianminfang[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: February 28, 2027
• Est. primary completion date: November 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• Disitamab vedotin
Disitamab Vedotin intravenously combined with radiotherapy (concurrent)

Locations

Country	Name	City	State
China	Shandong Cancer hospital &Institute	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
RemeGen Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT	Dose limiting toxicity (DLT)	First DV dose to 28 days after the last RT
Primary	AE	the incidence and severity of adverse events (AE);	First DV dose to 90 days after the last RT
Secondary	PK Characterize	The concentration of DV binding antibodies, total antibodies, and free MMAE.	Cycle1Day1 to Cycle1Day8 (each cycle is 14 days)
Secondary	Immunogenicity assessment	Anti-RC48 antibodies	Cycle1Day1 to Cycle1Day8 (each cycle is 14 days)
Secondary	ORR	(RECIST 1.1 standard, evaluated by investigators): objective response rate (ORR), the relationship between HER2 expression and therapeutic efficacy.	approximately 2 years from the first dose