Study of Disitamab Vedotin With Toripalimab Verus Disitamab Vedotin in Hormone Receptor Positive, HER2-low Locally Advanced or Metastatic Breast Cancer

NCT06105008 | Withdrawn Phase 2

• 1 other identifier: RC48-C033
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the efficacy, safety and tolerability of RC48-ADC with JS001 compared with RC48-ADC in endocrine-resistant hormone receptor (HR) positive, human epidermal growth factor receptor (HER)2-low advanced breast cancer.

Conditions

Breast Neoplasms

Keywords

HR+breast cancer; HER2-low breast cancer; advanced breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS), evaluated by investigator

  Defined as time from date of randomization until the date of objective radiological disease progression by investigator assessment according to RECIST v1.1 or death.

  Until progression or death, assessed up to approximately 36 months

Secondary Outcomes (9)

• Overall survival (OS)

  Until death, assessed up to approximately 36 months

• Objective Response Rate (ORR)

  Until progression, assessed up to approximately 36 months

• Disease Control Rate (DCR)

  Until progression, assessed up to approximately 36 months

• Duration of response (DoR)

  Until progression, assessed up to approximately 36 months

• Type, incidence, relatedness, severity, and seriousness of AEs

  Up to follow-up period, approximately 36 months

Study Arms (2)

Disitamab Vedotin + Toripalimab

EXPERIMENTAL

Disitamab Vedotin（RC48-ADC）with Toripalimab （JS001）arm

Drug: Disitamab Vedotin; Drug: Toripalimab

Disitamab Vedotin

ACTIVE COMPARATOR

Disitamab Vedotin（RC48-ADC） arm

Drug: Disitamab Vedotin

Interventions

Disitamab Vedotin DRUG

2.0 mg/kg intravenous (lV) infusion every 2 weeks

Also known as: RC48-ADC, DV

Disitamab Vedotin; Disitamab Vedotin + Toripalimab

Toripalimab DRUG

3.0 mg/kg intravenous (lV) infusion every 2 weeks

Also known as: JS001

Disitamab Vedotin + Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years and older years at the time of consent
• Pathologically confirmed breast cancer
• Stage III unresectable locally advanced or stage IV metastatic breast cancer.
• Subjects must be willing and able to provide recent non-previously radiotherapy metastases lesions (if feasible and available) to the sponsor-designated central laboratory prior to treatment initiation or, if not feasible or available, tumor tissue blocks (or fresh tissue sections, see laboratory manuals) obtained from locally recurrent lesions for biomarker analysis, including HER2 expression and HR status. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor lesion is required within 28 days prior to Cycle 1 Day 1. Biopsy must provide adequate tissue for analysis.
• Subjects must have HER2 low expression (defined as IHC 1+ or IHC 2+/ISH-) and HR+ status (defined as recent tumor showing ER and/or PR expression ≥1% \[according to ASCO/CAP 2020 guidelines\]) determined by the central laboratory.
• The subject must meet all of the following criteria:
• must not have received prior chemotherapy (including ADC) in the unresectable locally advanced or metastatic disease setting
• have undergone endocrine therapy, or patients with weak ER-positivity (1 to 10% nuclear positivity) were eligible if they were not candidates for endocrine therapy after an adequate assessment by the investigator
• disease recurrence or progression during adjuvant endocrine therapy period or within 12 months after completion of adjuvant endocrine therapy, either alone or in combination with CDK4/6 inhibitors, OR
• received prior endocrine therapy with documented disease progression during treatment period or thereafter in the unresectable locally advanced or metastatic disease setting, either alone or in combination with CDK4/6 inhibitors
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 assessed within 7 days prior to randomization.
• Measurable disease as defined in RECIST v1.1
• The following baseline laboratory data indicating adequate organ function:
• ANC ≥1,500/µL
• platelet count ≥100,000/μL

You may not qualify if:

• Known hypersensitivity to any excipient contained in the drug formulation of RC48-ADC, or pembrolizumab.
• Prior anti-HER2 therapy, including an ADC.
• Prior MMAE-containing agent
• Prior immunotherapy including anti-PD-(L)1 or anti-PD-(L)2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CD137, CTLA-4, OX-40) in the LA/m setting (\[neo\]adjuvant anti-PD-(L)1 is allowed if last dose is ≥12 months prior to recurrence or progression).
• History of another malignancy within 3 years prior to screening, with the exception of those with a negligible risk of metastasis or death (eg, approximate 5-year OS of ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• Subjects with known active CNS or leptomeningeal metastasis are excluded. Subjects with definitively treated brain metastasis (surgery and/or radiotherapy) are eligible if the following criteria are met:
• All known CNS lesions have been treated.
• No evidence of clinical and radiographic disease progression in the CNS for ≥4 weeks after definitive treatment.
• Neurological symptoms attributed to brain metastases have returned to baseline.
• No utilization of steroids to manage symptoms related to CNS disease or its treatment within 14 days of randomization. Anti-convulsant therapy is allowed if the dose has been stable for 14 days.
• Subjects with prior allogenic tissue/solid organ or bone marrow transplantation.
• Subjects with acute, chronic, or symptomatic infections, including:
• Active infection requiring systemic treatment ≤7 days before dose of study drug. Routine antimicrobial prophylaxis is permitted.
• Known positivity for hepatitis B (HBsAg positive with HBV DNA titers above the upper limit of normal), active hepatitis C infection (positive by polymerase chain reaction \[PCR\] or on antiviral therapy for hepatitis C within the last 6 months). Subjects who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks.
• Known history of seropositive Human Immunodeficiency Virus.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (3)

Binghe Xu

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

Location

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, China

Location

Hunan Cancer Hospital

Changsha, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

disitamab vedotin; toripalimab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jianmin Fang, Ph.D

  RemeGen Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 27, 2023
• Study Start: December 20, 2024
• Primary Completion: December 20, 2025
• Study Completion: April 10, 2026
• Last Updated: August 23, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)