A Study of RC48-ADC for the Treatment of HER2-expression Metastatic Breast Cancer With Abnormal Activation of PAM Pathway

NCT05331326 | Unknown Phase 2

• 1 other identifier: NCC3286
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, single-arm phase II clinical trial to evaluate the efficacy and safety of RC48 in metastatic human epidermal growth factor receptor 2 (HER2) expressing breast cancer with abnormal activation of PAM pathway.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate（ORR）

  Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• Overall Survival(OS)

  From date of randomization until the date of death from any cause, assessed up to 48 months

• Disease Control Rate (DCR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• Adverse events (AEs)

  Up to 2 years

• Tumor progression time (TTP)

  Up to 2 years

Study Arms (2)

HER2 Positive

EXPERIMENTAL

Drug: RC48-ADC 2.0 mg/kg (HER2 Positive) 32 advanced breast cancer participants with HER2 Positive will be treated with RC48-ADC at a dose of 2.0mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year.

Drug: RC48-ADC

HER2 Low Expression

EXPERIMENTAL

Drug: RC48-ADC 2.0 mg/kg (HER2 Low Expression) 32 advanced breast cancer participants with HER2 Low Expression will be treated with RC48-ADC at a dose of 2.0 mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year.

Drug: RC48-ADC

Interventions

RC48-ADC DRUG

RC48-ADC 2.0mg / kg, intravenous drip, once every 2 weeks

HER2 Low Expression; HER2 Positive

Eligibility Criteria

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

You may qualify if:

• Subjects aged ≥18 years (inclusive) and expected survival ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically and/or cytologically confirmed invasive locally advanced or metastatic breast cancer that is incurable and unresectable;
• HER2 expression (positive defined as: IHC 3+ or FISH+ and low expression defined as: IHC2+and FISH- or IHC 1+); previous test results of HER2 expression provided by the subjects (have to be confirmed by the investigator) and those obtained from the study site or the central laboratory were both acceptable;
• Genetic testing shows that the PAM（PI3K/Akt/mTOR）pathway related genes are mutated; previous test results provided by the subjects (have to be confirmed by the investigator) was both acceptable.
• No more than 1 lines of chemotherapy received after relapse/metastasis. The number of chemotherapy lines is restricted to chemotherapeutic drugs, and each chemotherapy regimen is counted as a number of chemotherapy line, excluding targeted drugs and/or endocrine drugs; the same maintenance treatment as the previous chemotherapy regimen will not be counted.
• Patients with HER2-positive metastatic breast cancer have received treatment with trastuzumab or its biosimilar (monotherapy or in combination with other drugs, such as for ≥ 3 months in the adjuvant therapy phase, and ≥ 6 weeks in the post-relapse and metastatic phase);
• With at least one measurable lesion per RECIST v1.1.
• Subjects may previously exposed to anthracyclines (e.g. doxorubicin, epirubicin) and/or taxanes (e.g., paclitaxel, docetaxel) including:
• has been pretreated in the adjuvant or neoadjuvant setting with anthracyclines and/or taxanes before breast cancer relapsing;
• has experienced treatment failure while receiving or after completing anthracycline- and/or taxane- based chemotherapy;
• not suitable for the choice of anthracycline- and/or taxane- based chemotherapy as first-line treatment in the judgment of investigator.
• Prior radiotherapy must have completed before randomization, with full recovery from acute radiation side effects. An interval of less than 4 weeks after radiotherapy was not allowed. Concurrent limited field radiation therapy (RT) is allowed. At least one measurable lesion must be completely outside the radiation portal in accordance with RECIST 1.1 guidelines.
• At least 30 days from major surgery before randomization, with full recovery.
• With Adequate Organ Function:

You may not qualify if:

• History of, or current active cancer other than breast cancer, with the exception of curatively resected non-melanomatous skin cancer, curatively treated cervical carcinoma in situ, or other primary solid tumors curatively treated with no known active disease present and no curative treatment administered for the last 3 years.
• Patients with medical conditions that the only manifestation is hydrothorax, ascites, bone lesions or other un-measurable diseases.
• Subjects with symptoms suggesting central nervous system (CNS) involvement or leptomeningeal metastases, any suspicious sins or symptoms of CNS involvement or leptomeningeal metastases should be excluded by CT or MRI scans.
• Other serious illness or medical conditions by the investigator during screening:
• Clinically significant cardiac disease; Unstable diabetes; Uncontrolled hypercalcemia; Clinically significant active infections (current or in the last two weeks). With history of active tuberculosis; Patients with active hepatitis B or C (HBsAg positive and HBV DNA positive; HCVAb positive).
• Previous organ allograft.
• Current peripheral neuropathy ≥grade 2 according to NCI version 4.0 criteria.
• Concomitant hormonal therapy for MBC.
• Ongoing anti-coagulation therapy.
• Presence of effusion in the third space (including massive hydrothorax or ascites) that cannot be controlled by drainage or other methods.
• Subjects of reproductive potential who are pregnant, breast feeding or not willing to use effective contraceptive precautions during the study and for at least one month after the last dose of investigational product in the judgment of the investigator.
• Patients with psychiatric disorder or other disease leading to incompliance to the therapy.
• An interval of less than 4 weeks between the last dose of previous chemotherapy and randomization.
• With prior treatment with T-DM1 or had participated in clinical studies with other ADCs.
• Treatment with any investigational drug within 30 days before the beginning of treatment with study drug. Less than 30 days since receipt of any other investigational product or device.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (3)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Beijing Huanxing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Cancer Hospital, Chinese Academy of Medical Sciences, Hebei Center

Langfang, Hebei, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Fei Ma

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fei Ma

CONTACT

86-10-87788060; drmafei@126.com

Hongnan Mo

CONTACT

86-10-87788120

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: April 15, 2022
• Study Start: April 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: August 1, 2024
• Last Updated: April 15, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)