Disitamab Vedotin in the Treatment With HER2- Expression, Subjects With Locally Advanced or Metastatic Castration-resistant Prostate Cancer

A Multicenter Open Phase II to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of Disitamab Vedotin in the Treatment With HER2- Expression, Subjects With Locally Advanced or Metastatic Castration-resistant Prostate Cancer

The purpose of this study is to evaluate the effectiveness of Disitamab Vedotin in the treatment of subjects with locally advanced or metastatic castration-resistant prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Disitamab Vedotin Injection

Detailed Description

This is a Multicenter Open Phase II to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of Disitamab Vedotin in the Treatment With HER2- Expression, Subjects with locally advanced or metastatic castration-resistant prostate cancer.

The study plans to enroll 40 subjects with locally advanced or metastatic CRPC with HER2 expression (IHC 1+ and above) who have been treated with androgen deprivation therapy and novel hormone therapy. Eligible subjects were enrolled and received RC48 intravenous infusion at a dose of 2.0 mg/kg every 2 weeks. Subjects received medication until disease progression, intolerable toxicity, active withdrawal, death, or study termination by the sponsor.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianmin Fang, Ph.D; Phone Number: +8610-58075763; Email: Jianminfang@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Principal Investigator: Jun Guo, Ph.D
      • Contact: Jun Guo, Ph.D
    • Beijing, Beijing, China, 100034
      • Not yet recruiting
      • Peking University First Hospital
      • Contact: Zhisong He, M.D
      • Principal Investigator: Zhisong He, M.D
    • Beijing, Beijing, China, 1000853
      • Not yet recruiting
      • The Third Medical Center of PLA General Hospital
      • Contact: Xu Zhang, M.D
      • Principal Investigator: Xu Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Pathology confirmed prostate adenocarcinoma
3. Locally advanced or metastatic prostate cancer
4. PCWG3 criteria-compliant prostate cancer progression occurs during androgen deprivation therapy (or bilateral scrotal excision). Progression will be determined based on at least 1 of the following criteria: PSA progression: defined as 2 consecutive increases in PSA, separated by at least 1 week, relative to the previous reference value. If a confirmed PSA increase is the only indicator of progression, then 1 ng/mL is the minimum starting value; Soft tissue progression: defined as an increase of ≥20% in the sum of the diameters of all target lesions (short-axis for lymph node lesions and long-axis for non-lymph node lesions) relative to the sum of the smallest diameters at the start of treatment or the presence of one or more new lesions; Bone lesion progression: defined as the detection of at least two additional new lesions on bone scan.
5. Serum testosterone level ≤ 50 ng/dL (or ≤ 1.73 nmol/L), prior to the first study drug administration;
6. Continuous androgen deprivation therapy (ADT) with LHRH agonists or LHRH antagonists or previous bilateral orchiectomy (surgical debridement) during the study period;
7. Confirmed HER2 expression (IHC 1+, 2+, 3+), HER2 gene amplification, or HER2 gene mutation;
8. Subjects were able to provide paraffin blocks or at least 5 paraffin embedded sections (white pieces) for HER2 detection, and the presence of HER2 expression was confirmed by central laboratory tests (immunohistochemistry 1+, 2+, 3+)；
9. Previous medical androgen deprivation therapy (or bilateral scrotal excision) and new hormone therapy (e.g. abiraterone, enzalutamide) and have developed disease progression

10. The following criteria should be met within 7 days prior to the first study dose:

    1. haemoglobin ≥ 9 g/dL;
    2. absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
    3. platelet count ≥ 100 × 109/L;
    4. serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
    5. without liver metastasis, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × ULN; with liver metastasis, alanine aminotransferase and aspartate aminotransferase ≤ 5 × ULN;;
    6. albumin (ALB) ≥ 25 g/L;
    7. blood creatinine ≤ 1.5 × ULN, or calculated according to the Cockcroft-Gault formula, creatinine clearance (CrCl) ≥ 50 mL/min;
    8. left ventricular ejection fraction (LVEF) ≥ 50%;
11. ECOG Physical Status Score of 0-1
12. Expected survival ≥ 6 months
13. Subjects whose spouses are of childbearing age must agree to use contraception during the study and for 6 months after the last dose; sperm donation is not permitted during the study and for 6 months after the last dose
14. Ability to understand and sign an informed consent form.

Exclusion Criteria:

1. Systematic chemotherapy, novel hormone therapy, targeted therapy, immunotherapy, or other antitumor therapy (including 5-alpha reductase inhibitors, oestrogens, and medroxyprogesterone, etc.)was administered prior to the initial study drug, and treatment ended within 5 half-lives (or 2 weeks, whichever is shorter) of the initial study drug. Except maintenance castration therapy (LHRH agonists or LHRH antagonists) or bone metastasis therapy(e.g., denosumab, zoledronic acid); In the first study, Chinese medicines with anti-tumor indications were used 2 weeks before administration.
2. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis (subjects who have been treated for brain metastases may be enrolled in this study provided they have stable disease [no evidence of progression as determined by imaging for at least 4 weeks prior to study dosing and and all neurological symptoms have fully recovered], there is no evidence of new or enlarging brain metastases, and discontinuation of steroid therapy at least 7 days prior to the first dose of the trial treatment. (This exception does not include carcinomatous meningitis, which should be excluded regardless of whether it is clinically stable or not).
3. Has received anti-HER2 therapy ;
4. Major surgery, systemic radiotherapy or biologic therapy within 4 weeks prior to first study drug administration, or minor surgery or local radiotherapy within 1 week prior to enrollment;
5. Toxicity due to prior antineoplastic therapy that has not recovered to Common Terminology Criteria for Adverse Events (CTCAE Version 5.0) Grade 1 or below, with the exception of alopecia and abnormalities in laboratory tests or toxicity associated with LHRH agonists or LHRH antagonists that are not considered by the investigator to pose a safety risk;
6. Known allergic reactions to components of the study treatment or its analogues
7. Diagnosis of other malignancies that are expected to affect life expectancy or may interfere with disease assessment. Except for cured non-melanoma skin cancer and superficial bladder cancer
8. Severe and/or persistent infection within 14 days prior to starting the study drug
9. Serum virological tests: positive HBsAg test result with a positive HBV DNA copy number; positive HCVAb test result; positive HIVAb test result;
10. Known serious cardiovascular disease, including any of the following: myocardial infarction, thrombotic event, or unstable angina pectoris in the past 3 months; chronic heart failure, New York Heart Association (NYHA) class II or higher; presence of unstable arrhythmia; uncontrolled hypertension;
11. Combined grade 2 and higher (CTCAE version 5.0) peripheral neuropathy
12. Presence of other systemic diseases that, in the judgement of the investigator, are not under stable control, including diabetes mellitus, liver cirrhosis, pneumonitis, and obstructive pulmonary disease;
13. In the judgement of the investigator, there were other circumstances that made participation in the study unsuitable.

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: Disitamab Vedotin; Disitamab Vedotin Q2W arm	Drug: Disitamab Vedotin Injection; 2.0 mg/kg, intravenous infusion，D1, every 2 weeks is a treatment cycle; Other Names: DV,RC48

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression free survival，rPFS	Define imaging disease progression according to RECIST v1.1 (for all lesions except bone lesions) or PCWG3 (for bone lesions) as the time from the first dose of the drug to the time when the imaging shows disease progression or death.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of laboratory tests abnormalities	To be summarized using descriptive statistics	Up to follow-up period, approximately 2 years
Incidence of ECG abnormalities	To be summarized using descriptive statistics	Up to follow-up period, approximately 2 years
Percentage of Participants With Adverse Events (AEs)	Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v5.0	Up to approximately 2 years
Objective remission rate (ORR)	ORR assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1)	Up to approximately 2 years
Disease Control Rate (DCR)	Percentage of patients with complete response, partial response, or stable disease for a certain period of time according to RECIST v1.1.	Until progression, assessed up to approximately 2 years
Time to PSA progression(TTPP)	Defined as time from date of first dose to first PSA progression	Until progression, assessed up to approximately 2 years
Duration of response (DoR)	Defined as the time from the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression by Investigators assessment according to RECIST 1.1	Until progression, assessed up to approximately 2 years
PSA response rate	Percent of subjects with different degree of decrease in PSA compared to baseline	Until progression, assessed up to approximately 2 years
Time to first symptomatic bone-related event (SSE)	Defined as the time from the first dose to the first occurrence of SSE.	Until progression, assessed up to approximately 2 years
Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death from any cause.	Up to approximately 2 years
Cmax of RC48	Peak Plasma Concentration of RC48	Up to approximately 2 years
AUC of RC48	Area under the plasma concentration versus time curve of RC48	Up to approximately 2 years
AUC of MMAE	Area under the plasma concentration versus time curve of MMAE	Up to approximately 2 years
Immunogenicity of RC48	Anti-drug antibody (ADA) of RC48 positive samples, etc.	up to approximately 2 years

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Study Director: Jianmin Fang, Ph.D, RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic Castration-resistant prostate cancer.; HER2- expression
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Disitamab vedotin
• Other Study ID Numbers: RC48-C034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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